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Sample records for ageing rat brain

  1. Changes in intracellular calcium in brain cells of aged rats

    Institute of Scientific and Technical Information of China (English)

    Yu Li; Yunpeng Cao

    2008-01-01

    BACKGROUND: Studies have shown that voltage-dependent calcium influx, and enhancement of certain calcium-dependent processes in neurons, is related to aging. OBJECTIVE: To observe changes in intracellular calcium ([Ca2+]i) in neurons of aged rats, and to compare with young rats. DESIGN, TIME AND SETTING: A randomized control experiment of neurophysiology was performed at the Central Laboratory of School of Pharmaceutical Science, China Medical University from June to August 2004. MATERIALS: Ten male, healthy, Wistar rats, 19 months old, were selected for the aged group. Ten male, 3-month-old, Wistar rats were selected for the young control group. Fura-2/AM was provided by the Institute of Pharmaceutical Research of Chinese Academy of Medical Sciences, and the F-2000 fluorospectrophotometer was a product of Hitachi, Japan. METHODS: Fluorescence Fura-2 spectrophotometer was used to measure [Ca2+]i in acutely dissociated brain cells of aged and young rats. The concentration of extracellular potassium was controlled by adding different volumes of chloridated potassium solution of high concentration. MAIN OUTCOME MEASURES: [Ca2+]i in neurons of young and aged rats in the presence of 1 mmol/L extracellular calcium concentration and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium. Absolute increase of [Ca2+]i in neurons of young and aged rats when extraceUular potassium was 5,10,20, 40 mmol/L. RESULTS: In the presence of 1 mmol/L extracellular Ca2+ and 0 mmol/L (resting state), 5, 10, 20, and 40 mmol/L extracellular potassium, [Ca2+]i in the neurons of aged rats was significantly less than that in young rats (P 0.05). CONCLUSION: The overload of [Ca2+]i in neurons of aged rats is greater than that of young rats under the same circumstances.

  2. Differential Expression of Sirtuins in the Ageing Rat Brain

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    Gilles J. Guillemin

    2015-05-01

    Full Text Available Although there are seven mammalian sirtuins (SIRT1-7, little is known about their expression in the ageing brain. To characterise the change(s in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of ‘physiologically’ aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy ageing.

  3. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

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    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  4. Fertility, aging and the brain neuroendocrinological studies in female rats

    NARCIS (Netherlands)

    Franke, A.N.

    2003-01-01

    It is well known that fertility decreases in female mammals with advancing age. In women this decrease already starts around the age of 30 and shows a large variation between individuals. The aim of this thesis was to elucidate changes in the reproductive system, especially in the brain, that may un

  5. Restoration of brain protein synthesis in mature and aged rats by a DA agonist, piribedil.

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    Bustany, P; Trenque, T; Crambes, O; Moulin, M

    1995-01-01

    Brain ageing affects numerous cerebral metabolic pathways such as cerebral glucose consumption or protein synthesis rate. The pharmacological effect of a mixed D1-D2 dopaminergic agonist, piribedil, on this last metabolism is reported. Cerebral Protein Synthesis Rate (CPSR) was measured by the [35S]L-methionine autoradiographic procedure in 38 main brain regions of 11 and 26-month-old Wistar rats after a 2-month treatment per os at 9 and 30 mg/kg/day with piribedil. Mean decrease of CPSR was -21% during the 15-month ageing we followed, with important local variations. Mean CPSR increased with the two treatments, +25% in mature and +35% in aged rats. Treatments restored CPSR of aged rats to the exact mature subjects levels in quite all the brain regions. No dose-effect or asymetrical modification was statistically revealed for the two treatments. Metabolic increases involved particularly central brain gray structures, especially some DA-targeted brain nuclei concerned with behaviour and learning. This effect argued for a general metabotrophic effect of D1-D2 dopamine stimulation of the brain. The original pattern of local ageing of brain protein synthesis in rat was also incidentally reported. This was the first direct report of a wide and effective metabolic activation of CPSR in the brain during ageing by a curative dopaminergic agonist treatment.

  6. Age-related changes in reactive oxygen species production in rat brain homogenates.

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    Driver, A S; Kodavanti, P R; Mundy, W R

    2000-01-01

    The generation of reactive oxygen species (ROS) and resultant oxidative stress have been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases or exposure to environmental chemicals. We have investigated intrinsic age-related differences in the ability of the various brain regions to generate ROS in the absence and presence of Fe(2)+. ROS production in crude brain homogenates from adult rats was linear with respect to time and tissue concentration, and was stimulated to a greater extent by Fe(2)+ than was TBARS production. ROS production was then determined in homogenates from cerebral cortex, striatum, hippocampus, and cerebellum of 7-day-old, 14-day-old, 21-day-old, adult (3-6-month old), and aged (24-month-old) rats using the fluorescent probe 2',7'-dichlorodihydrofluorescin (DCFH). Basal levels of ROS production were similar in 7-, 14-, and 21-day olds, increased in adults, and highest in aged rats, and did not differ between brain regions. ROS production was stimulated by Fe(2)+ (0. 3-30 microM) in a concentration-dependent manner in all brain regions. However, the stimulation of ROS production by Fe(2)+ varied with age. ROS production was greater in 14- and 21-day-old rats compared with adult and aged animals. ROS production in 7-day-old rats was decreased at low Fe(2)+ concentrations and increased at high Fe(2)+ concentrations compared to adult and aged rats. These data show that brain homogenates from neonatal rats respond differently to Fe(2)+, and suggest that developing animals may be more sensitive to oxidative stress in the brain after exposure to toxicants. Published by Elsevier Science Inc.

  7. Astaxanthin alleviates brain aging in rats by attenuating oxidative stress and increasing BDNF levels.

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    Wu, Wanqiang; Wang, Xin; Xiang, Qisen; Meng, Xu; Peng, Ye; Du, Na; Liu, Zhigang; Sun, Quancai; Wang, Chan; Liu, Xuebo

    2014-01-01

    Astaxanthin (AST) is a carotenoid pigment which possesses potent antioxidative, anti-inflammatory, and neuroprotective properties. The aim of this study was to investigate whether administration of AST had protective effects on D-galactose-induced brain aging in rats, and further examined its protective mechanisms. The results showed that AST treatment significantly restored the activities of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD), and increased glutathione (GSH) contents and total antioxidant capacity (T-AOC), but decreased malondialdehyde (MDA), protein carbonylation and 8-hydroxy-2- deoxyguanosine (8-OHdG) levels in the brains of aging rats. Furthermore, AST increased the ratio of Bcl-2/Bax, but decreased the expression of Cyclooxygenase-2 (COX-2) in the brains of aging rats. Additionally, AST ameliorated histopathological changes in the hippocampus and restored brain derived neurotrophic factor (BDNF) levels in both the brains and hippocampus of aging rats. These results suggested that AST could alleviate brain aging, which may be due to attenuating oxidative stress, ameliorating hippocampus damage, and upregulating BDNF expression.

  8. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

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    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  9. In vivo and in vitro assessment of brain bioenergetics in aging rats.

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    Vančová, Ol'ga; Bačiak, Ladislav; Kašparová, Svatava; Kucharská, Jarmila; Palacios, Hector H; Horecký, Jaromír; Aliev, Gjumrakch

    2010-11-01

    Brain energy disorders can be present in aged men and animals. To this respect, the mitochondrial and free radical theory of aging postulates that age-associated brain energy disorders are caused by an imbalance between pro- and anti-oxidants that can result in oxidative stress. Our study was designed to investigate brain energy metabolism and the activity of endogenous antioxidants during their lifespan in male Wistar rats. In vivo brain bioenergetics were measured using ³¹P nuclear magnetic resonance (NMR) spectroscopy and in vitro by polarographic analysis of mitochondrial oxidative phosphorylation. When compared to the young controls, a significant decrease of age-dependent mitochondrial respiration and adenosine-3-phosphate (ATP) production measured in vitro correlated with significant reduction of forward creatine kinase reaction (kfor) and with an increase in phosphocreatine (PCr)/ATP, PCr/Pi and PME/ATP ratio measured in vivo. The levels of enzymatic antioxidants catalase, GPx and GST significantly decreased in the brain tissue as well as in the peripheral blood of aged rats. We suppose that mitochondrial dysfunction and oxidative inactivation of endogenous enzymes may participate in age-related disorders of brain energy metabolism.

  10. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  11. Age-related changes of metallothionein 1/2 and metallothionein 3 expression in rat brain.

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    Scudiero, Rosaria; Cigliano, Luisa; Verderame, Mariailaria

    2017-01-01

    Neurodegeneration is one of the main physiological consequences of aging on brain. Metallothioneins (MTs), low molecular weight, cysteine-rich proteins that bind heavy-metal ions and oxygen-free radicals, are commonly expressed in various tissues of mammals. MTs are involved in the regulation of cell proliferation and protection, and may be engaged in aging. Expression of the ubiquitous MTs (1 and 2) and the brain specific MT3 have been studied in many neurodegenerative disorders. The research results indicate that MTs may play important, although not yet fully known, roles in brain diseases; in addition, data lack the ability to identify the MT isoforms functionally involved. The aim of this study was to analyse the level of gene expression of selected MT isoforms during brain aging. By using real-time PCR analysis, we determined the MT1/2 and MT3 expression profiles in cerebral cortex and hippocampus of adolescent (2months), adult (4 and 8months), and middle-aged (16months) rats. We show that the relative abundance of all types of MT transcripts changes during aging in both hippocampus and cortex; the first effect is a generalized decrease in the content of MTs transcripts from 2- to 8-months-old rats. After passing middle age, at 16months, we observe a huge increase in MT3 transcripts in both cortical and hippocampal areas, while the MT1/2 mRNA content increases slightly, returning to the levels measured in adolescent rats. These findings demonstrate an age-related expression of the MT3 gene. A possible link between the increasing amount of MT3 in brain aging and its different metal-binding behaviour is discussed.

  12. Oxidative stress induces the decline of brain EPO expression in aging rats.

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    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (pEPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (pEPO (r=-0.701, pEPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability.

  13. Expression of alpha-synuclein in different brain parts of adult and aged rats.

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    Adamczyk, A; Solecka, J; Strosznajder, J B

    2005-03-01

    The synucleins are a family of presynaptic proteins that are abundant in neurons and include alpha-, beta, and gamma-synuclein. Alpha-synuclein (ASN) is involved in several neurodegenerative age-related disorders but its relevance in physiological aging is unknown. In the present study we investigated the expression of ASN mRNA and protein in the different brain parts of the adult (4-month-old) and aged (24-month-old) rats by using RT-PCR technique and Western blot, respectively. Our results indicated that mRNA expression and immunoreactivity of ASN is similar in brain cortex, hippocampus and striatum but markedly lower in cerebellum comparing to the other brain parts. Aging lowers ASN mRNA expression in striatum and cerebellum by about 40%. The immunoreactivity of ASN in synaptic plasma membranes (SPM) from aged brain cortex, hippocampus and cerebellum is significantly lower comparing to adult by 39%, 24% and 65%, respectively. Beta-synuclein (BSN) was not changed in aged brain comparing to adult. Age-related alteration of ASN may affect the nerve terminals structure and function.

  14. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.;

    2000-01-01

    of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... and degradation of NAPE, respectively. The results showed that 1) the ability to accumulate NAPE during post-decapitative ischemia is especially high in the youngest rats and is markedly reduced in older brains [in 1-day-old rat brains NAPE accumulated to 1.5% of total phospholipids, while in 30-day-old rat......N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...

  15. Antiaging Effect of Metformin on Brain in Naturally Aged and Accelerated Senescence Model of Rat.

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    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-01-09

    Metformin, a biguanide, is a widely used antidiabetic drug, which inhibits gluconeogenesis and is used to treat hyperglycemia in type 2 diabetes. Through activation of AMPK (AMP-activated protein kinase) pathway, metformin also mimics caloric restriction health benefits. Aging causes substantial molecular to morphological changes in brain, the brain cells being more susceptible toward oxidative stress mediated damages due to the presence of high lipid content and higher oxygen consumption. Wistar rats (naturally aged and d-galactose induced rat model) were supplemented with metformin (300 mg/kg b.w. orally) for 6 weeks. The biomarkers of oxidative stress such as antioxidant capacity (ferric reducing antioxidant potential [FRAP]), malondialdehyde (MDA), reduced glutathione (GSH), protein carbonyl (PCO), reactive oxygen species (ROS), acetylcholinesterase (AChE) activity, and nitric oxide (NO) were measured in brain tissues of control and experimental groups. The results indicate that metformin treatment augmented the levels of FRAP and GSH in naturally aged, and d-gal induced aging model groups compared to the respective controls. In contrast, metformin treated groups exhibited significant reduction in MDA, PCO, ROS, and NO levels and a significant increase in AChE activity in induced aging rats. The administration of d-galactose upregulated the expression of sirtuin-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) and downregulated the expression of Beclin-1. Metformin supplementation downregulated the d-galactose induced expressions of sirtuin-2, IL-6, and TNF-α expression, whereas upregulated the Beclin-1 expression. Our data confirm that metformin restores the antioxidant status and improves healthy brain aging through the activation of autophagy and reduction in inflammation.

  16. Gender- and region-dependent changes of redox biomarkers in the brain of successfully aging LOU/C rats.

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    Moyse, Emmanuel; Arseneault, Madeleine; Gaudreau, Pierrette; Ferland, Guylaine; Ramassamy, Charles

    2015-07-01

    The LOU/C (LOU) rat is an obesity resistant strain with higher longevity and healthspan than common rats. The management of oxidative stress being important to successful aging, we characterized this process in the aging LOU rat. Male/female LOU rats were euthanized at 4, 20, and 29 months. Macrodissected hippocampus, striatum, parietal cortex, cerebellum were assayed for tissue concentrations of glutathione (GSH), gamma-glutamyl-cysteine-synthetase (γ-GCS), total thiols, protein carbonyls, mRNAs of clusterin and the known protective enzymes thioredoxine-1 (TRX-1), glutaredoxine-1 (GLRX-1), superoxide dismutase-1 (SOD-1). Brain levels of GSH, γ-GCS, total thiols remained constant with age, except for GSH and γ-GCS which decreases in females. Clusterin, TRX-1, GLRX-1, SOD-1 mRNA levels were maintained or increased in the hippocampus with age. Age-dependency of the markers differed between sexes, with SOD-1 and TRX-1 decreases out of hippocampus in females. Since antioxidants were reported to decrease with age in the brain of Wistar rats, maintenance of GSH levels and of protective enzymes mRNA levels in the LOU rat brain could contribute to the preservation of cognitive functions in old age. Altogether, the successful aging of LOU rats may, at least in part, involve the conservation of functional antioxidant mechanisms in the brain, supporting the oxidative stress theory of aging.

  17. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

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    Bachstetter, Adam D; Pabon, Mibel M; Cole, Michael J; Hudson, Charles E; Sanberg, Paul R; Willing, Alison E; Bickford, Paula C; Gemma, Carmelina

    2008-01-01

    Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC) given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain. PMID:18275610

  18. Peripheral injection of human umbilical cord blood stimulates neurogenesis in the aged rat brain

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    Sanberg Paul R

    2008-02-01

    Full Text Available Abstract Background Neurogenesis continues to occur throughout life but dramatically decreases with increasing age. This decrease is mostly related to a decline in proliferative activity as a result of an impoverishment of the microenvironment of the aged brain, including a reduction in trophic factors and increased inflammation. Results We determined that human umbilical cord blood mononuclear cells (UCBMC given peripherally, by an intravenous injection, could rejuvenate the proliferative activity of the aged neural stem/progenitor cells. This increase in proliferation lasted for at least 15 days after the delivery of the UCBMC. Along with the increase in proliferation following UCBMC treatment, an increase in neurogenesis was also found in the aged animals. The increase in neurogenesis as a result of UCBMC treatment seemed to be due to a decrease in inflammation, as a decrease in the number of activated microglia was found and this decrease correlated with the increase in neurogenesis. Conclusion The results demonstrate that a single intravenous injection of UCBMC in aged rats can significantly improve the microenvironment of the aged hippocampus and rejuvenate the aged neural stem/progenitor cells. Our results raise the possibility of a peripherally administered cell therapy as an effective approach to improve the microenvironment of the aged brain.

  19. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

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    Nicolas Martin

    Full Text Available Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence. We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  20. Aging Brain, Aging Mind.

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    Selkoe, Dennis J.

    1992-01-01

    Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

  1. Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats.

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    Krivova, Natalia A; Zaeva, Olga B; Grigorieva, Valery A

    2015-01-01

    The Morris water maze (MWM) is a tool for assessment of age-related modulations spatial learning and memory in laboratory rats. In our work was investigated the age-related decline of MWM performance in 11-month-old rats and the effect exerted by training in the MWM on the redox mechanisms in rat brain parts. Young adult (3-month-old) and aged (11-month-old) male rats were trained in the MWM. Intact animals of the corresponding age were used as the reference groups. The level of pro- and antioxidant capacity in brain tissue homogenates was assessed using the chemiluminescence method. A reduced performance in the MWM test was found in 11-month-old rats: at the first day of training they showed only 30% of successful MWM trials. However, at the last training day the percentage of successful trials was equal for young adult and aged animals. This indicates that the aged 11-month-old rats can successfully learn in MWM. Therewith, the MWM spatial learning procedure itself produces changes in different processes of redox homeostasis in 11-month-old and 3-month-old rats as compared to intact animals. Young adult rats showed a decrease in prooxidant capacity in all brain parts, while 11-month-old rats demonstrated an increase in antioxidant capacity in the olfactory bulb, pons + medulla oblongata and frontal lobe cortex. Hence, the MWM procedure activates the mechanisms that restrict the oxidative stress in brain parts. The obtained results may be an argument for further development of the animal training procedures aimed to activate the mechanisms that can prevent the age-related deterioration of performance in the learning test. This may be useful not only for the development of training procedures applicable to human patients with age-related cognitive impairments, but also for their rehabilitation.

  2. Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor.

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    Calabrese, Francesca; Guidotti, Gianluigi; Racagni, Giorgio; Riva, Marco A

    2013-12-01

    Aging is a physiological process characterized by a significant reduction of neuronal plasticity that might contribute to the functional defects observed in old subjects. Even if the neurobiological mechanisms that contribute to such impairment remain largely unknown, a role for neurotrophic molecules, such as the neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On this basis, the purpose of this study was to provide a detailed investigation of the BDNF system, at transcriptional and translational levels, in the ventral and dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats, compared with in adult animals. The expression of major players in BDNF regulation and response, including the transcription factors, calcium-responsive transcription factor, cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed. Our results demonstrate that the BDNF system is affected at different levels in aged rats with global impairment including reduced transcription, impaired protein synthesis and processing, and decreased activation of the TrkB receptors. These modifications might contribute to the cognitive deficits associated with aging and suggest that pharmacological strategies aimed at restoring reduced neurotrophism might be useful to counteract age-related cognitive decline.

  3. Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing.

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    Yin, Lanxuan; Sun, Yubai; Wu, Jinfeng; Yan, Siyu; Deng, Zhenglu; Wang, Jun; Liao, Shenke; Yin, Dazhong; Li, Guolin

    2015-02-01

    Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

  4. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

    Science.gov (United States)

    Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C; Morgan, Todd E; Finch, Caleb E; Pike, Christian J; Mack, Wendy J; Cadenas, Enrique; Brinton, Roberta D

    2015-07-01

    The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's.

  5. In vivo molecular imaging of the GABA/benzodiazepine receptor complex in the aged rat brain.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2012-07-01

    The GABA-ergic system, known to regulate neural tissue genesis during cortical development, has been postulated to play a role in cerebral aging processes. Using in vivo molecular imaging and voxel-wise quantification, we aimed to assess the effects of aging on the benzodiazepine (BDZ) recognition site of the GABA(A) receptor. To visualize BDZ site availability, [(11)C]-flumazenil microPET acquisitions were conducted in young and old rats. The data were analyzed and region of interest analyses were applied to validate the voxel-wise approach. We observed decreased [(11)C]-flumazenil binding in the aged rat brains in comparison with the young control group. More specifically, clusters of reduced radioligand uptake were detected in the bilateral hippocampus, cerebellum, midbrain, and bilateral frontal and parieto-occipital cortex. Our results support the pertinence of voxel-wise quantification in the analysis of microPET data. Moreover, these findings indicate that the aging process involves declines in neural BDZ recognition site availability, proposed to reflect alterations in GABA(A) receptor subunit polypeptide expression.

  6. Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months

    Directory of Open Access Journals (Sweden)

    Chiu Catherine

    2012-01-01

    Full Text Available Abstract Background Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD and is seen in normal aging. Alterations in cerebrospinal fluid (CSF dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Aβ accumulation in the aging rat brain. Methods Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Aβ40 and Aβ42 concentrations in the cortex and hippocampus were measured by ELISA. Results There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p p p p -1 to 12 months (11.30 day-1 and then a decrease to 20 months (10.23 day-1 and 30 months (6.62 day-1. Aβ40 and Aβ42 concentrations in brain increased from 3-30 months (p Conclusions In young rats there is no correlation between CSF turnover and Aβ brain concentrations. After 12 months, CSF turnover decreases as brain Aβ continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.

  7. Spatial memory training modifies the expression of brain-derived neurotrophic factor tyrosine kinase receptors in young and aged rats.

    Science.gov (United States)

    Silhol, M; Arancibia, S; Maurice, T; Tapia-Arancibia, L

    2007-05-25

    Aging leads to alterations in the function of the hippocampus, a brain structure largely involved in learning processes. This study aimed at examining the basal levels and the impact of a learning-associated task on brain-derived neurotrophic factor (BDNF), on BDNF full-length catalytic receptor (TrkB.FL) and on the truncated forms (TrkB.T1 and TrkB.T2) receptor expression (mRNA and protein) in the hippocampus of young (2-month-old) and aged (24-month-old) Wistar rats. Spatial memory was evaluated using a water-maze procedure involving visible and invisible platform location learning. Aged rats showed higher latencies during the first two training days but rapidly exhibited learning performances similar to patterns observed with young rats. Real-time PCR measurements showed that aged rats had significantly higher levels of trkB.FL mRNAs than young rats under basal conditions. In situ hybridization analysis indicated that the highest level of trkB.FL mRNA (mRNA encoding for TrkB.FL receptor) was noted in the dentate gyrus, and in the CA2 and CA3 hippocampal layers. In contrast, there was no marked difference in trkB.T1 signal in any hippocampal region. Training induced a significant reduction in trkB.FL mRNA levels solely in aged rats. In contrast, in young and aged rats, trkB.T2 mRNA levels were significantly increased after training. Measurements of proteins revealed that learning significantly increased TrkB.FL content in aged rats. Untrained aged rats presented higher levels of BDNF and brain-derived neurotrophic factor precursor (proBDNF) proteins than young rats. Training strongly increased precursor BDNF metabolism in young and aged rats, resulting in increased levels of proBDNF in the two groups but in old rats the mature BDNF level did not change. This study shows that Wistar rats present age-related differences in the levels of BDNF and TrkB isoforms and that spatial learning differentially modifies some of these parameters in the hippocampus.

  8. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Science.gov (United States)

    Ho, Yuen-Shan; Yang, Xifei; Yeung, Sze-Chun; Chiu, Kin; Lau, Chi-Fai; Tsang, Andrea Wing-Ting; Mak, Judith Choi-Wo; Chang, Raymond Chuen-Chung

    2012-01-01

    Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  9. Cigarette smoking accelerated brain aging and induced pre-Alzheimer-like neuropathology in rats.

    Directory of Open Access Journals (Sweden)

    Yuen-Shan Ho

    Full Text Available Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD. To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP processing by increasing the production of sAPPβ and accumulation of β-amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia.

  10. Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Data.gov (United States)

    U.S. Environmental Protection Agency — Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups. This dataset is associated with the following...

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

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Royland, Joyce E. [Genetic and Cellular Toxicology Branch, Integrated Systems Toxicology Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Richards, Judy E. [Research Core Unit, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Besas, Jonathan; MacPhail, Robert C. [Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2011-11-15

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

  12. Effects of Early Onset of Nimodipine Treatment on Microvascular Integrity in the Aging Rat Brain

    NARCIS (Netherlands)

    de Jong, Giena; Horváth, E.; Luiten, P.G.M.

    1990-01-01

    We studied the effects of long-term treatment with 1,4-dihydropyridine nimodipine on age-related changes of the cerebral microvasculature in layers I, III, and V of the frontoparietal motor cortex of aged (30 months) male Wistar rats. Ultrastructural alterations of microvessels can either be attribu

  13. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

    Science.gov (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M

    2013-01-01

    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  14. Age-related changes in kynurenic acid production in rat brain

    DEFF Research Database (Denmark)

    Gramsbergen, J B; Schmidt, W; Turski, W A

    1992-01-01

    investigated in tissue slices and was found to be significantly enhanced in the cortex and hippocampus of old animals. The effect of depolarizing agents or sodium replacement was virtually identical in tissues from young and old rats. These data, which are in excellent agreement with reports on an age...

  15. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Science.gov (United States)

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  16. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    Directory of Open Access Journals (Sweden)

    Kun Hua

    Full Text Available Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like

  17. Calcium antagonists decrease capillary wall damage in aging hypertensive rat brain

    NARCIS (Netherlands)

    Farkas, E.; de Jong, G.I.; Apro, E.; Keuker, J.I.H.; Luiten, P.G.M.

    2001-01-01

    Chronic hypertension during aging is a serious threat to the cerebral vasculature. The larger brain arteries can react to hypertension with an abnormal wall thickening, a loss of elasticity and a narrowed lumen. However, little is known about the hypertension-induced alterations of cerebral capillar

  18. The Oral Iron Chelator, Deferasirox, Reverses the Age-Dependent Alterations in Iron and Amyloid-β Homeostasis in Rat Brain: Implications in the Therapy of Alzheimer's Disease.

    Science.gov (United States)

    Banerjee, Priyanjalee; Sahoo, Arghyadip; Anand, Shruti; Bir, Aritri; Chakrabarti, Sasanka

    2016-01-01

    The altered metabolism of iron impacts the brain function in multiple deleterious ways during normal aging as well as in Alzheimer's disease. We have shown in this study that chelatable iron accumulates in the aged rat brain along with overexpression of transferrin receptor 1 (TfR1) and ferritin, accompanied by significant alterations in amyloid-β (Aβ) peptide homeostasis in the aging brain, such as an increased production of the amyloid-β protein precursor, a decreased level of neprilysin, and increased accumulation of Aβ42. When aged rats are given daily the iron chelator, deferasirox, over a period of more than 4 months starting from the 18th month, the age-related accumulation of iron and overexpression of TfR1 and ferritin in the brain are significantly prevented. More interestingly, the chelator treatment also considerably reverses the altered Aβ peptide metabolism in the aging brain implying a significant role of iron in the latter phenomenon. Further, other results indicate that iron accumulation results in oxidative stress and the activation of NF-κB in the aged rat brain, which are also reversed by the deferasirox treatment. The analysis of the results together suggests that iron accumulation and oxidative stress interact at multiple levels that include transcriptional and post-transcriptional mechanisms to bring about changes in the expression levels of TfR1 and ferritin and also alterations in Aβ peptide metabolism in the aging rat brain. The efficacy of deferasirox in preventing age-related changes in iron and Aβ peptide metabolism in the aging brain, as shown here, has obvious therapeutic implications for Alzheimer's disease.

  19. Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex.

    Science.gov (United States)

    Frenzel, Monika; Rommelspacher, Hans; Sugawa, Michiru D; Dencher, Norbert A

    2010-08-01

    Activity and stability of life-supporting proteins are determined not only by their abundance and by post-translational modifications, but also by specific protein-protein interactions. This holds true both for signal-transduction and energy-converting cascades. For vital processes such as life-span control and senescence, to date predominantly age-dependent alterations in abundance and to lesser extent in post-translational modifications of proteins are examined to elucidate the cause of ageing at the molecular level. In mitochondria of rat cortex, we quantified profound changes in the proportion of supramolecular assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS electrophoresis and fluorescent staining. Complex I was present solely in supercomplexes and those lacking complex IV were least stable in aged animals (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age-associated degradation by an overall decline in abundance of 1.5-fold for the monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation.

  20. Evidence for novel age-dependent network structures as a putative primo vascular network in the dura mater of the rat brain

    Institute of Scientific and Technical Information of China (English)

    Ho-Sung Lee; Dai-In Kang; Seung Zhoo Yoon; Yeon Hee Ryu; Inhyung Lee; Hoon-Gi Kim; Byung-Cheon Lee; Ki Bog Lee

    2015-01-01

    With chromium-hematoxylin staining, we found evidence for the existence of novel age-depen-dent network structures in the dura mater of rat brains. Under stereomicroscopy, we noticed that chromium-hematoxylin-stained threadlike structures, which were barely observable in 1-week-old rats, were networked in specific areas of the brain, for example, the lateral lobes and the cerebella, in 4-week-old rats. In 7-week-old rats, those structures were found to have become larger and better networked. With phase contrast microscopy, we found that in 1-week-old rats, chromium-hematoxylin-stained granules were scattered in the same areas of the brain in which the network structures would later be observed in the 4- and 7-week-old rats. Such age-depen-dent network structures were examined by using optical and transmission electron microscopy, and the following results were obtained. The scattered granules fused into networks with increas-ing age. Cross-sections of the age-dependent network structures demonstrated heavily-stained basophilic substructures. Transmission electron microscopy revealed the basophilic substructures to be clusters with high electron densities consisting of nanosized particles. We report these data as evidence for the existence of age-dependent network structures in the dura mater, we discuss their putative functions of age-dependent network structures beyond the general concept of the dura mater as a supporting matrix.

  1. Effects of total paeony glucosides on mRNA expressions of Toll receptors and interleukin-33 in the brain tissue of D-galactose induced aging rats:an experimental research

    Institute of Scientific and Technical Information of China (English)

    张海燕

    2013-01-01

    Objective To investigate effects of total paeony glucosides (TPGs) on the expressions of Toll receptors (TLR4) and interleukin-33 (IL-33) in the brain tissue of D-galactose-induced aging rats.Methods Fifty SD rats

  2. Effect of propofol on brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus of aged rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Qiang Fu; Jiangbei Cao; Weidong Mi

    2012-01-01

    We intraperitoneally injected 10 and 50 mg/kg of propofol for 7 consecutive days to treat a rat model of chronic cerebral ischemia. A low-dose of propofol promoted the expression of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element binding protein, and cAMP in the hippocampus of aged rats with chronic cerebral ischemia, but a high-dose of propofol inhibited their expression. Results indicated that the protective effect of propofol against cerebral ischemia in aged rats is related to changes in the expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus, and that the cAMP-cAMP responsive element binding protein pathway is involved in the regulatory effect of propofol on brain-derived neurotrophic factor expression.

  3. The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na+, K+-, Mg2+-ATPase activities, antioxidant status, and learning performance of aged rats

    Directory of Open Access Journals (Sweden)

    Haris Carageorgiou

    2008-09-01

    Full Text Available Haris Carageorgiou1, Antonios C Sideris1, Ioanna Messari1, Chrissoula I Liakou1, Stylianos Tsakiris21Department of Pharmacology, 2Department of Physiology, Medical School, University of Athens, Athens, GreeceAbstract: We investigated the effects of rivastigmine (a cholinesterase inhibitor and selegiline ((-deprenyl, an irreversible inhibitor of monoamineoxidase-B, alone and in combination, on brain acetylcholinesterase (AChE, (Na+, K+-, Mg2+-ATPase activities, total antioxidant status (TAS, and learning performance, after long-term drug administration in aged male rats. The possible relationship between the biochemical and behavioral parameters was evaluated.Methods: Aged rats were treated (for 36 days with rivastigmine (0.3 mg/kg rat/day ip, selegiline (0.25 mg/kg rat/day im, rivastigmine plus selegiline in the same doses and way of administration as separately. Aged and adult control groups received NaCl 0.9% 0.5 ml ip.Results: TAS was lower in aged than in adult rats, rivastigmine alone does not affect TAS, decreases AChE activity, increases (Na+, K+-ATPase and Mg2+-ATPase activity of aged rat brain and improves cognitive performance. Selegiline alone decreases free radical production and increases AChE activity and (Na+, K+-ATPase activity, improving cognitive performance as well. In the combination: rivastigmine seems to cancel selegiline action on TAS and AChE activity, while it has additive effect on (Na+, K+-ATPase activity. In the case of Mg2+-ATPase selegiline appears to attenuate rivastigmine activity. No statistically significant difference was observed in the cognitive performance.Conclusion: Reduced TAS, AChE activity and learning performance was observed in old rats. Both rivastigmine and selesiline alone improved performance, although they influenced the biochemical parameters in a different way. The combination of the two drugs did not affect learning performance.Keywords: aged rat, brain enzymes, TAS, learning, rivastigmine

  4. Decline in cytochrome c oxidase activity in rat-brain mitochondria with aging. Role of peroxidized cardiolipin and beneficial effect of melatonin.

    Science.gov (United States)

    Petrosillo, Giuseppe; De Benedictis, Valentina; Ruggiero, Francesca M; Paradies, Giuseppe

    2013-10-01

    Reactive oxygen species (ROS) are considered a key factor in mitochondrial dysfunction associated with brain aging process. Mitochondrial respiration is an important source of ROS and hence a potential contributor to brain functional changes with aging. In this study, we examined the effect of aging on cytochrome c oxidase activity and other bioenergetic processes such as oxygen consumption, membrane potential and ROS production in rat brain mitochondria. We found a significant age-dependent decline in the cytochrome c oxidase activity which was associated with parallel changes in state 3 respiration, membrane potential and with an increase in H2O2 generation. The cytochrome aa3 content was practically unchanged in mitochondria from young and aged animals. The age-dependent decline of cytochrome c oxidase activity could be restored, in situ, to the level of young animals, by exogenously added cardiolipin. In addition, exposure of brain mitochondria to peroxidized cardiolipin resulted in an inactivation of this enzyme complex. It is suggested that oxidation/depletion of cardiolipin could be responsible, at least in part, for the decline of cytochrome c oxidase and mitochondrial dysfunction in brain aging. Melatonin treatment of old animals largely prevented the age-associated alterations of mitochondrial bioenergetic parameters. These results may prove useful in elucidating the molecular mechanisms underlying mitochondrial dysfunction associated with brain aging process, and may have implications in etiopathology of age-associated neurodegenerative disorders and in the development of potential treatment strategies.

  5. Age-related alteration of activity and gene expression of endothelial nitric oxide synthase in different parts of the brain in rats.

    Science.gov (United States)

    Strosznajder, Joanna B; Jeśko, Henryk; Zambrzycka, Agata; Eckert, Anne; Chalimoniuk, Małgorzata

    2004-11-11

    Nitric oxide (NO) plays important roles in aging and neurodegeneration. Our previous results indicated that aging differently affects NOS isoforms. Expression of nNOS mRNA was lower while iNOS was absent at any age. However, total NO synthesis increased in aged cerebral cortex and cerebellum as a consequence of changes of nNOS phosphorylation state. The question arise how aging influences activity and expression of eNOS in different parts of adult and aged brain. The levels of eNOS mRNA, protein and activity were measured using RT-PCR, immuno- and radiochemical methods, respectively. Our studies indicated that after inhibition of nNOS with 7-nitroindazole (7-NI) NO synthesis is lower in all parts of aged brain comparing to adults. However, eNOS activity significantly decreases only in cerebellum. The expression of eNOS determined on mRNA level was enhanced in all investigated aged brain parts to 140-190% of adult value and the data were statistically significant for cerebral cortex and cerebellum. The higher level of mRNA is probably the adaptive response to lower NOS activity. However, the Western-blot signal of eNOS protein was unchanged in aged brain parts comparing to adults suggesting age-related disturbances of protein synthesis and its function. It is also possible that a post-translational modification of the enzyme occurs in the aged rat brain. The lower eNOS activity in aged brain may significantly affects the signal transduction processes on the pathway NO/cGMP/PKG.

  6. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

    Science.gov (United States)

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cereb...

  7. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  8. EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  9. Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN) expression in frontal cortex and hippocampus of aged rat treated with high tryptophan diet.

    Science.gov (United States)

    Musumeci, Giuseppe; Castrogiovanni, Paola; Castorina, Sergio; Imbesi, Rosa; Szychlinska, Marta Anna; Scuderi, Soraya; Loreto, Carla; Giunta, Salvatore

    2015-10-01

    Age-related cognitive decline is accompanied by an alteration in neurotransmitter synthesis and a dysregulation of neuroplasticity-related molecules such as serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP) enriched diet protect against memory deficits during physiological aging. Since 5-HT is closely associated to BDNF, we aimed to investigate the effect of high TrP diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus (Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic diet (1 month) containing high TrP significantly prevents age-related decline of BDNF protein expression in both brain areas as indicated by ELISA and Western Blot analyses. Interestingly, immunohistochemical analyses confirmed that high TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both brain areas tested and this correlated with BDNF increase in the FC and hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these finding provide evidence that enhanced TrP intake and the consequent increase in 5-HT neurotransmission may act as a modulator of BDNF system suggesting a possible mechanism for the protective role of serotonergic system on memory impairment occurring along normal aging process.

  10. TOXICITY PATHWAY ANALYSIS IN AGING BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental stressors is poorly understood. To investigate the contribution of different life stages on response to toxicants, we examined the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.3...

  11. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE

    Science.gov (United States)

    The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), i...

  12. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in brain cells in vitro

    Science.gov (United States)

    The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defense in brain is a critical factor in the declining neural functions and cognitive deficits accompanying age. In aging, there are noticeable alterations in the membrane microenvironment,...

  13. AGE-INDEPENDENT, GREY-MATTER-LOCALIZED, BRAIN ENHANCED OXIDATIVE STRESS IN MALE FISCHER 344 RATS,1,2

    Science.gov (United States)

    While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex...

  14. Cognition and brain functional aging

    Directory of Open Access Journals (Sweden)

    Hui-jie LI

    2014-03-01

    Full Text Available China has the largest population of elderly adults. Meanwhile, it is one of the countries showing fastest aging speed in the world. Aging processing is always companied with a series of brain structural and functional changes, which result in the decline of processing speed, working memory, long-term memory and executive function, etc. The studies based on functional magnetic resonance imaging (fMRI found certain aging effects on brain function activation, spontaneous activity and functional connectivity in old people. However, few studies have explored the brain functional curve during the aging process while most previous studies explored the differences in the brain function between young people and old people. Delineation of the human brain functional aging curve will promote the understanding of brain aging mechanisms and support the normal aging monitoring and early detection of abnormal aging changes. doi: 10.3969/j.issn.1672-6731.2014.03.005

  15. Effects of ginsenoside on brain-derived neurotrophic factor and tyrosine kinase B mRNA expression in the hippocampal formation of aged rats

    Institute of Scientific and Technical Information of China (English)

    Hong Lai; Wensu Liu; Zhaosheng Li; Haihua Zhao; Yongli Lü

    2008-01-01

    BACKGROUND:There are a limited number of studies involving the effects of ginsenosides,the active component of ginseng,on expression of hippocampal TrkB mRNA in aged rats.OBJECTIVE:To observe expression of brain-derived neurotrophic factor(BDNF) and tyrosine kinase B (TrkB)mRNA in the hippocampal formation of aged rats,as well as changes after ginsenoside administrated.DESIGN,TIME AND SETTING:A randomized,controlled experiment was performed at the Department of Anatomy,College of Basic Medical Sciences,China Medical University in March 2005.MATERIALS:A total of 39 female,Wistar rats were randomly divided into 3 groups (n=13 each):young (3-5 months old),aged(27 months old),and ginsenoside group(received 25mg/kg/d ginsenoside in the drinking water between 17 and 27 months of age).METHODS:Following anesthesia,the rats were exsanguinated and perfused transcardially with chilled,heparinized,0.9% saline.The brains were removed and post-fixed in 40 g/L paraformaldehyde/phosphate buffer for 20 minutes,and further incubated in 30% sucrose/phosphate buffer overnight.MAIN OUTCOME MEASURES:In situ hybridization,immunohistochemistry,and image analysis were used to investigate expression of BDNF and Trk(B mRNA in the hippocampal formation.RESULTS:The expression levels of BDNF in the hippocampal CA3 and CA1 of aged rats was significantly less than the young group(t=2.879,1.814,1.984,P<0.05).BDNF expression was significantly greater in the dentate gyrus of the ginsenoside group,compared with the aging group(t=1.943,P<0.01).The expression of TrkB mRNA in the hippocampal CA3,CA1,and dentate gyrus of aged rats was less than the young group(t=3.540,3.629,17.905,P<0.01).TrkB mRNA expression in the CA3 region and dentate gyrus of the ginsenoside group was significantly greater compared with the aging group(t=1.293,3.386,P<0.05.0.01).CONCLUSION:BDNF and TrkB mRNA expression in the hippocampal formation were reduced in the aged group.However,ginsenosides can increase BDNF and TrkB m

  16. In aging, the vulnerability of rat brain mitochondria is enhanced due to reduced level of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) and subsequently increased permeability transition in brain mitochondria in old animals.

    Science.gov (United States)

    Krestinina, Olga; Azarashvili, Tamara; Baburina, Yulia; Galvita, Anastasia; Grachev, Dmitry; Stricker, Rolf; Reiser, Georg

    2015-01-01

    Aging is accompanied by progressive dysfunction of mitochondria associated with a continuous decrease of their capacity to produce ATP. Mitochondria isolated from brain of aged animals show an increased mitochondrial permeability transition pore (mPTP) opening. We recently detected new regulators of mPTP function in brain mitochondria, the enzyme 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and its substrates 2', 3'-cAMP and 2', 3'-cNADP, and the neuronal protein p42(IP4). Here, we compared parameters of mPTP opening in non-synaptic brain mitochondria isolated from young and old rats. In mitochondria from old rats (>18 months), mPTP opening occurred at a lower threshold of Ca(2+) concentration than in mitochondria from young rats (aging was accompanied by decreased levels of voltage-dependent anion channel (VDAC; by 69%) and of p42(IP4) (by 59%). Thus, reduced levels of CNP in mitochondria could lead to a rise in the concentration of the mPTP promoter 2', 3'-cAMP. The level of CNP and p42(IP4) and, probably VDAC, might be essential for myelination and electrical activity of axons. We propose that in aging the reduction in the level of these proteins leads to mitochondrial dysfunction, in particular, to a decreased threshold Ca(2+) concentration to induce mPTP opening. This might represent initial steps of age-related mitochondrial dysfunction, resulting in myelin and axonal pathology.

  17. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.

    Science.gov (United States)

    Paredes, Sergio D; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A F

    2015-01-01

    Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

  18. Effect of Ligustrazine and Shenmai Injection on ATPase and free radical metabolism in the aged rats with myocardial injury after brain ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the protecitve mechanism of Ligustrazine (LT), Shenmai Parenteral Injection (SPI), combination of Ligustrazine and Shenmai Parenteral Injection (LSP) to myocardial injury after brain ischemia-reperfusion in aged rats from the change in ATPase and free radical in order to provide theoretical basic for prevention and cure of cerebral infarction. METHODS: Aged rats (more than 20 months) were divided into model group, control group, Nimotop group, LT group, SPI group and LSP group. We measured the following items in aged rats with 60 min of reperfusion after 30 min of brain ischemia: the content of MDA, the activities of superoxide dismutase (SOD), lactic dehydrrogenase (LDH), creatine phosphokinase (CPK), ATPase. RESUTLS: The CPK and LDH activities in the model rats increased obviously. The serum CPK activity in the LSP group, the LT group, nimotop group was lower than those in the model group obviously. The serum LDH activities in LT group and SPI group were obviously lower compared with those in the model group. The activity of Na+-K+-ATPase and Ca2+-ATPase in model group was decreased. Contrast to the model group, the activity of Na+-K+-ATPase in LSP group, Nimotop group, LT group and the activities of Ca2+-ATPase in the LSP group were higher. The serum MDA/SOD ratio was larger than that in the control group. The decrease in myocardial SOD activity and the increase in the MDA level, MDA/SOD ratio in the model group showed significant difference compared with that in the control. The MDA level in the LSP group was lower than that in the model group. The increase in myocardial SOD activity and decrease in MDA, MDA/SOD ratio were obvious in the LSP group compared with the model group. CONCLUSION: The myocardial injury after brain ischemia-reperfusion in aged rats was related to the decrease in the activity of Na+-K+-ATPase and injury of free radical. LT, SPI, LSP and Nimotop could prevent this inury. Nimotop and LT could enhanced the

  19. nNOS expression of hippocampal neurons in aged rats after brain ischemia/reperfusion and its role in DND development

    Institute of Scientific and Technical Information of China (English)

    杨传红; 赖晃文; 詹纯列; 肖育华; 郑文岭

    2002-01-01

    To study the role of neuronal nitric oxide synthase (nNOS) in aged rats' hippocampal delayed neuronal death (DND) following brain ischemia. Methods: Models of incomplete brain ischemia were induced by clipping common carotid artery. A total of 46 aged SD rats were divided into 8 groups: normal control group ( Group A, n = 5 ), sham-operation group ( Group B, n = 5), reperfusion 1, 6, 12, 24, 48, and 96 hours groups after brain ischemia for 30 minutes ( Group C, D,E, F, G, and H, n = 6/group). The expression of nNOS was examined by immunohistochemistry and neuronal ultrastructural changes were observed by the transmission electron microscopy (TEM) at different time points after reperfusion. Results: Immunohistochemistry showed that nNOS expression in the hippocampal neurons was high in Group E, iow expression in Group D, moderate expression in Group F and G. There was nearly no expression of nNOS in Group A, B, C, and H. UItrastructure of hippocampal neurons was damaged more severely in reperfusion over 24 hours groups. Conclusions: Nitric oxide (NO) may be one of the important factors in inducing DND after ischemia/reperfusion.

  20. Brain aging and therapeutic interventions

    DEFF Research Database (Denmark)

    This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic...

  1. Nutrients, Microglia Aging, and Brain Aging.

    Science.gov (United States)

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  2. H2O2-mediated DNA damage and repair in the brain cells in the aging rats detected by comet assay

    Institute of Scientific and Technical Information of China (English)

    Suming ZhangM.D., Ph.D; Zongchao Han, M.D.; Siyu Fang, M.D.; Ruan Yang, M.D; Wei Wang, M.D., Ph. D

    2000-01-01

    Objective: To identify the relation between DNA damage susceptibility/ DNA repair capability and aging process after insults, an observation of H2O2_induced DNA damage and the kinetics of DNA repair in senescent murine brain cells with the alkaline single cell gel electrophoresis (SCGE/Comet assay) was made. Methods: The dissociated brain cells harvested in the area of the cerebral cortex, hippocampus, basal gang]ion from 3-month (n=10), 8-month (n=8) and 26-month (n=5) old rats were respectively treated with H2O2 in gradient doses for 10 min, or without H2O2 as controls. The cells embedded in agarose were lysed, helix-untied, electrophoresed, stained with a fluorescence DNA binding stain, viewed under a fluorescence microscope. Individual image was optically recorded. The frequency of the tailed cells and the grade of tails wereused to analyze single strand breaks of DNA and injury intensity. Results: By the cell and DNA image like comets, a linear increase was noticed in vulnerability of DNA both to H2O2 doses and to the age. Regarding the damaged region of the brain, the cortex cells were more vulnerable to the insult than the hippocampus/basal ganglionic cells. Whatever aging or not the cells were, the maximum of ratio of DNA repair was only within 1 hour during the incubation for 0.5-4 hours after the insults. Furthermore, the more aging, the less ratio of DNA repair of sick cells. Conclusion: The DNA damagesusceptibility and the DNA repair capability of individual cells, whatever its age is, can be detected by this brain cell injury model. Comet assay is a sensitive way to find out DNA damage and repair of the cells. It should be more difficult for the cells to cope with an acute and excessive than with a persistent, chronic and mild DNA damage which is more related to an accumulating injury, the aging.

  3. Influence of ginsenoside on expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in the medial septum of aged rats

    Institute of Scientific and Technical Information of China (English)

    Liang Zeng; Haihua Zhao; Yongli Lü; Wenbo Dai

    2008-01-01

    BACKGROUND: It has been shown that ginsenoside, the effective component of ginseng, can enhance expression of choline acetyl transferase, as well as brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB), in cholinergic neurons of the basal forebrain.OBJECTIVE: To qualitatively and quantitatively verify the influence of ginsenoside on expression of BDNF and its receptor, TrkB, in the medial septum of aged rats, and to provide a molecular basis for clinical application.DESIGN, TIME AND SETTING: A contrast study, which was performed in the Department of Anatomy, China Medical University, and the Department of Anatomy, Shenyang Medical College between December 2005 and May 2007.MATERIALS: Thirty-five, healthy, female, Sprague Dawley rats were selected for this study. Ginsenoside (81% purity) was provided by Jilin Ji'an Wantai Chinese Medicine Factory; anti-BDNF antibody, anti-TrkB antibody, and their kits were provided by Wuhan Boster Company.METHODS: A total of 35 rats were divided into three groups: young (four months old), aging (26 months old), and ginsenoside. Rats in the ginsenoside group were administered ginsenoside (25mg/kg/d) between 17 months and 26 months.MAIN OUTCOME MEASURES: Immunohistochemistry and in situ hybridization were used to measure expression of BDNF and TrkB in the medial septum of aged rats, and the detected results were expressed as gray values.RESULTS: ①Qualitative detection: using microscopy, degenerative neurons were visible in the medial septum in the aging group. However, neuronal morphology in the ginsenoside group was similar to neurons in the young group.②Quantitative detection: the mean gray value of BDNF-positive and TrkB-positive products in the aging group were significantly higher than in the young group (t=3.346,4.169, P<0.01); however, the mean gray value in the ginsenoside group was significantly lower than in the aging group (t=2.432,2.651, P<0.01).CONCLUSION: Ginsenoside can increase

  4. The Effect of Aging on Mitochondrial Complex I and the Extent of Oxidative Stress in the Rat Brain Cortex.

    Science.gov (United States)

    Tatarkova, Zuzana; Kovalska, Maria; Timkova, Veronika; Racay, Peter; Lehotsky, Jan; Kaplan, Peter

    2016-08-01

    One of the characteristic features of the aging is dysfunction of mitochondria. Its role in the regulation of metabolism and apoptosis suggests a possible link between these cellular processes. This study investigates the relationship of respiratory complex I with aging-related oxidative stress in the cerebral mitochondria. Deterioration of complex I seen in senescent (26-months old) mitochondria was accompanied by decline in total thiol group content, increase of HNE and HNE-protein adducts as well as decreased content of complex I subunits, GRIM-19 and NDUFV2. On the other hand, decline of complex I might be related with the mitochondrial apoptosis through increased Bax/Bcl-2 cascade in 15-month old animal brains. Higher amount of Bcl-2, Bcl-xL with the lower content of GRIM-19 could maintain to some extent elevated oxidative stress in mitochondria as seen in the senescent group. In the cortical M1 region increased presence of TUNEL+ cells and more than 20-times higher density of Fluoro-Jade C+ cells in 26-months old was observed, suggesting significant neurodegenerative effect of aging in the neuronal cells. Our study supports a scenario in which the age-related decline of complex I might sensitize neurons to the action of death agonists, such as Bax through lipid and protein oxidative stimuli in mitochondria. Although aging is associated with oxidative stress, these changes did not increase progressively with age, as similar extent of lesions was observed in oxidative stress markers of the both aged groups.

  5. Brain size, sex, and the aging brain.

    Science.gov (United States)

    Jäncke, Lutz; Mérillat, Susan; Liem, Franziskus; Hänggi, Jürgen

    2015-01-01

    This study was conducted to examine the statistical influence of brain size on cortical, subcortical, and cerebellar compartmental volumes. This brain size influence was especially studied to delineate interactions with Sex and Age. Here, we studied 856 healthy subjects of which 533 are classified as young and 323 as old. Using an automated segmentation procedure cortical (gray and white matter [GM and WM] including the corpus callosum), cerebellar (GM and WM), and subcortical (thalamus, putamen, pallidum, caudatus, hippocampus, amygdala, and accumbens) volumes were measured and subjected to statistical analyses. These analyses revealed that brain size and age exert substantial statistical influences on nearly all compartmental volumes. Analyzing the raw compartmental volumes replicated the frequently reported Sex differences in compartmental volumes with men showing larger volumes. However, when statistically controlling for brain size Sex differences and Sex × Age interactions practically disappear. Thus, brain size is more important than Sex in explaining interindividual differences in compartmental volumes. The influence of brain size is discussed in the context of an allometric scaling of the compartmental volumes.

  6. Effects of chronic forced swim stress on hippocampal brain-derived neutrophic factor (BDNF) and its receptor (TrkB) immunoreactive cells in juvenile and aged rats.

    Science.gov (United States)

    Badowska-Szalewska, Ewa; Spodnik, Edyta; Klejbor, Ilona; Morys, Janusz

    2010-01-01

    A type of stress stimulation and age are claimed to affect the expression of brain-derived neurotrophic factor (BDNF) and its receptor - tyrosine kinase B (TrkB) in the hippocampal regions differentially. This study aimed to explore the influence of chronic (15 min daily for 21 days) forced swim stress (FS) exposure on the BDNF and TrkB containing neurons in the hippocampal CA1, CA3 pyramidal cell layers and dentate gyrus (DG) granule cell layer in juvenile (P28) and aged (P360) rats. An immunofluorescence (-ir) method was used to detect BDNF-ir and TrkB-ir cells. Under chronic FS exposure, in the group of juvenile rats a significant decrease in the density of BDNF immunoreactive neurons was observed in CA1 and DG (P less than CA3, where it remained unaltered just as the density of TrkB-ir cells in CA1 and DG, but in CA3 the number of TrkB-ir cells was found to grow (P less than 0.05) in comparison with control groups. After chronic FS exposure of aged (P360) rats, the density of BDNF-ir and TrkB-ir cells did not decline in any of the subregions of the hippocampus. In all subfields of the hippocampus, the denseness of BDNF-positive neurons was significantly higher in P360 stressed group, compared with P28 stressed group, but the density of TrkB-ir fell more markedly in P360 than in P28. In conclusion, chronic FS stress influenced the number of BDNF and TrkB immunoreactive neurons only in juvenile animals. The age of rats tested in the chronic forced swim test was a decisive factor determining changes in the density of BDNF-ir and TrkB-ir in the hippocampal structures.

  7. Aging, Brain Size, and IQ.

    Science.gov (United States)

    Bigler, Erin D.; And Others

    1995-01-01

    Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

  8. Effect of endotoxin on brain cell apoptotic in aging rats%内毒素对老龄大鼠脑细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    赵楠; 韩柏; 韩德五; 李夏青

    2012-01-01

    目的 探讨内毒素对老龄大鼠脑细胞凋亡的影响.方法 观察正常以及门静脉注射内毒素后24月龄、6月龄大鼠血浆内毒素与TNF-α水平的变化;体外观察内毒素和TNF-α对脑细胞胞浆游离钙的影响,通过流式细胞仪检测脑细胞凋亡情况.结果 正常与注射内毒素后24月龄大鼠血浆内毒素水平均显著高于6月龄大鼠(t=3.684,P<0.05;t=4.583,P<0.05),而TNF-α明显升高仅见于注射内毒素后(t=7.766,P<0.001);TNF-α可使脑细胞胞浆游离钙明显升高(t=2.668,t=73.589,t =4.641,P<0.05);发现门静脉注射内毒素的24月龄、6月龄大鼠均发生脑细胞凋亡(50.53%,29.60%).结论 老龄大鼠血浆内毒素升高,致使脑细胞胞浆游离钙升高、细胞凋亡发生,这可能与细胞因子改变脑细胞微生态环境有关.%Objective To study the effect of endotoxin on brain cell apoptotic in aging rats.Methods Endotoxin and TNF-α content of plasma were determined in normal and after endotoxin infection of 24 months old and 6 month old rats.Effect of endotoxin and TNF-α on free Ca2 + in brain cells were observed in vitro,and apoptosis of brain cells were examined by FCM.Results The level of endotoxin in plasma were much higher in 24 months old rats than those of 6 months old rats in both normal and after endotoxin injection groups,but TNF-α was increased significantly only after endotoxin injection.TNF-α was elevated significantly free Ca2 + in brain cells,and after endotoxin injection via portal vein apoptosis of brain cells were developed.Conclusions Increased plasma endotoxin toxin and TNF-α in 24 months old rats contributed to elevation of Ca2 + in brain cells and apoptosis,and the mechanism might involves changes of brain microecological environment induced by altered cytokine.

  9. Biology of aging brain

    Directory of Open Access Journals (Sweden)

    Shankar S

    2010-10-01

    Full Text Available Normal aging of the nervous system is associated with some degree of decline in a number of cognitive functions. With the present day attempts to increase the life span, understanding the metabolic interactions and various mechanisms involved in normal neuronal aging continues to be a challenge. Loss of neurons is now recognized to be more modest than the initial estimates suggested and the loss only affected some of the specific neuroanatomical areas like hippocampus and prefrontal cortex. Individual neurons in addition show reduced size of dendritic and axonal arborization. Neurons have significant homeostatic control of the essential physiological functions like synaptic excitability, gene expression and metabolic regulation. Deviation in these normal events can have severe consequences as observed in aging and neurodegeneration. Based on experimental evidence, the evolution of aging is probably the result of altered metabolic triad: the mitochondria, reactive oxygen species and intracellular calcium homeostasis. Perturbations in the metabolic and functional state of this triad lead to a state of decreased homeostatic reserve, where the aged neurons still could maintain adequate function during normal activity. However, these neurons become vulnerable to the stress of excessive metabolic loads associated with spells of ischemia, trauma progressing to neuronal degeneration. Age-related neuronal dysfunction probably involves a host of subtle changes involving the synapses, receptors, neurotransmitters, cytological alterations, electrical transmission, leading to cognitive dysfunction. An exaggeration of it could be the clinical manifestation of dementia, with intraneuronal accumulation of protein aggregates deranging the metabolic state. This review deals with some of the structural, functional and metabolic features of aging nervous system and discusses briefly the functional consequences.

  10. Long-term treatment of aged Long Evans rats with a dietary supplement containing neuroprotective peptides (N-PEP-12) to prevent brain aging: effects of three months daily treatment by oral gavage.

    Science.gov (United States)

    Hutter-Paier, B; Reininger-Gutmann, B; Wronski, R; Doppler, E; Moessler, H

    2015-01-01

    Aging is associated with morphological and functional changes in the brain, resulting in the deterioration of cognitive performance. Growth factors like BDNF are suggested to be involved in the regulation of age-related processes in the brain. A novel dietary supplement produced from purified nerve cell proteins, N-PEP-12, has shown to share properties with naturally occurring peptide growth factors by stimulating neurite outgrowth and beneficial effects on neuronal survival and protection against metabolic stress in cell cultures. The current study investigates the effects of long-term intake on age-dependent memory decline by assessing cognitive performance and synaptic density. All the experiments were performed in aged Long Evans rats randomly assigned to saline or N-PEP-12 once daily by gavage over a period of three months. Behavioral tests were performed in the Morris Water Maze after one, two and three months of treatment. Histological examinations were performed in the hippocampal formation and in the entorhinal cortex by measuring the synaptic density. This study shows that the oral intake of N-PEP-12 has beneficial effects on the cognitive performance of aged animals and that these effects go along with an increase in the synaptic density. Thus, N-PEP-12 may help maintain memory and learning performance during the aging process.

  11. Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats

    Directory of Open Access Journals (Sweden)

    Zhengqian eLi

    2016-04-01

    Full Text Available Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD. Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2 and -9 (MMP-9, as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3, and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II and Ang II receptor type 1 (AT1 after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1, as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor.

  12. Aging and functional brain networks

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi D.; Tomasi, D.; Volkow, N.D.

    2011-07-11

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

  13. Brain networks in aging and dementia

    NARCIS (Netherlands)

    Hafkemeijer, A.

    2016-01-01

    This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological aging, with differences in network degeneration between different types of dementia. These disease-specific network

  14. Brain aging, Alzheimer's disease, and mitochondria

    OpenAIRE

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the ...

  15. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    Science.gov (United States)

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  16. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

    Science.gov (United States)

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  17. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    Science.gov (United States)

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  18. Staying Socially Active Nourishes the Aging Brain

    Science.gov (United States)

    ... fullstory_163679.html Staying Socially Active Nourishes the Aging Brain Researchers suggest making friends of all ages ... and Human Services. More Health News on: Healthy Aging Recent Health News Related MedlinePlus Health Topics Healthy ...

  19. MORPHOLOGICAL CHANGES IN THE HIPPOCAMPUS OF RATS IN ACCELERATED AGING

    Directory of Open Access Journals (Sweden)

    K. Yu. Maksimova

    2014-01-01

    Full Text Available The aim of this work was the analysis of structural changes with age in the hippocampus of senescenceaccelerated OXYS rats when signs of accelerated brain aging are missing (age 14 days, developments (age 5 months, and active progresses (age 15 months. The study was performed on 15 OXYS rats and 15 Wistar rats (as a control. After dislocation, brains were dissected, fixed with 10% formalin, embedded in paraffin, and serially cut in coronal sections (5μm thickness. These sections were stained with Cresyl violet and examined with a photomicroscope (Carl Zeiss Axiostar plus, Germany. The total number of hippocampal pyramidal cells in the CA1, CA3 and the dentate gyrus regions were estimated in 14-dayold, 5and 15-month-old OXYS and Wistar rats (n = 5 on the 5 slices of each brain sections. The number of neurons with chromatolysis, hyperchromatic with darkly stained cytoplasm and shrunken neurons were calculated as degenerative neurons. The pictures obtained with the program Carl Zeiss Axio Vision 8.0 with increasing 10  100, determined the average area bodies and nuclei of neurons (mkm2. The significant structural changes of neurons in the CA1, CA3 and dentate gyrus regions of the hippocampus in OXYS rats at 5 month of age are revealed by light microscopy. This results indicates the early develop neurodegeneration in OXYS rats. The most pronounced morphological changes occur in the CA1 region of the hippocampus of OXYS rats and irreversible. The degenerative changes of neurons in the hippocampus increases by the age of 15 months. Morphometric analysis of the average area of bodies and the nuclei of hippocampal neurons in CA1, CA3 and the dentate gyrus regions of OXYS and Wistar rats at 14 days of age showed no significant interline differences. At 5 months of age in the CA1 region of the hippocampus of OXYS rats was determined a significantly lower average body size and nuclei of pyramidal neurons compared with Wistar rats. With age, these

  20. Cellular senescence and the aging brain.

    Science.gov (United States)

    Chinta, Shankar J; Woods, Georgia; Rane, Anand; Demaria, Marco; Campisi, Judith; Andersen, Julie K

    2015-08-01

    Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies.

  1. Structural imaging measures of brain aging.

    Science.gov (United States)

    Lockhart, Samuel N; DeCarli, Charles

    2014-09-01

    During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

  2. Antioxidative defense mechanisms in the aging brain

    Directory of Open Access Journals (Sweden)

    Jovanović Zorica

    2014-01-01

    Full Text Available Aging is an extremely complex, multifactorial process that is characterized by a gradual and continuous loss of physiological functions and responses, particularly marked in the brain. A common hallmark in aging and age-related diseases is an increase in oxidative stress and the failure of antioxidant defense systems. Current knowledge indicates that the level of glutathione progressively declines during aging. Because nerve cells are the longest-living cells that exhibit a high consumption rate of oxygen throughout an individual’s lifetime, the brain may be especially vulnerable to oxidative damage and this vulnerability increases during aging. In addition, the brain contains high concentrations of polyunsaturated fatty acids and transition metals and low antioxidative defense mechanisms. Although aging is an inevitable event, a growing volume of data confirms that antioxidant supplementation in combination with symptomatic drug treatments reduces oxidative stress and improves cognitive function in aging and age-related diseases. The present review discusses the neuroprotective effects of antioxidants in the aging brain.

  3. Aging and brain rejuvenation as systemic events.

    Science.gov (United States)

    Bouchard, Jill; Villeda, Saul A

    2015-01-01

    The effects of aging were traditionally thought to be immutable, particularly evident in the loss of plasticity and cognitive abilities occurring in the aged central nervous system (CNS). However, it is becoming increasingly apparent that extrinsic systemic manipulations such as exercise, caloric restriction, and changing blood composition by heterochronic parabiosis or young plasma administration can partially counteract this age-related loss of plasticity in the aged brain. In this review, we discuss the process of aging and rejuvenation as systemic events. We summarize genetic studies that demonstrate a surprising level of malleability in organismal lifespan, and highlight the potential for systemic manipulations to functionally reverse the effects of aging in the CNS. Based on mounting evidence, we propose that rejuvenating effects of systemic manipulations are mediated, in part, by blood-borne 'pro-youthful' factors. Thus, systemic manipulations promoting a younger blood composition provide effective strategies to rejuvenate the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged CNS as a means to rejuvenate regenerative, synaptic, and cognitive functions late in life, with potential implications even for extending lifespan. We review evidence of brain rejuvenation focusing on several systemic manipulations - exercise, caloric restriction, heterochronic parabiosis, and young plasma administration - and their ability to restore regenerative capacity, synaptic plasticity, and cognitive function in the brain.

  4. Cardiovascular and hemodynamic contribution to brain aging

    NARCIS (Netherlands)

    Sabayan, Behnam

    2014-01-01

    In summary, chapter 1 of this thesis provides a background on the demographic, biologic and cardiovascular aspects of brain aging. Chapter 2 shows that higher blood pressure is associated with lower cognitive decline in very old age. Findings of Chapter 3 indicate that higher blood pressure is assoc

  5. The effects of sex on brain iron status in rats

    Institute of Scientific and Technical Information of China (English)

    HAO Qian; CHANG Yanzhong

    2015-01-01

    Objective:Iron plays essential roles in the human body. Studies have shown that iron is dis-tributed differently in male and female Rats in liver, spleen, bone marrow, kidney, heart. However, the effects of sex on iron distribution in central nervous system are not well established. Methods:To explore the effects of the above mentioned, in this study, female and male Sprague Dawley rats were used at 4 months of age. The synthesis of ferritin light chain (FTL), transferrin receptor1 (TfR1), ferroportin 1 (FPN1), divalent metal transporter 1 ( DMT1) in the cortex, hippocampus, striatum, cerebellum, and olfactory bulb was determined by Western blot a-nalysis. Results:The results showed that the levels of FTL protein in the cortex, hippocampus, striatum, cerebel-lum, and olfactory bulb were higher in female rats than in male rats, but the levels of TfR1 protein were lower in female rats than in male rats. There was no significant change in FPN1 and DMT1 expression in brain. Conclu-sions:These data suggest that sex have effects on brain iron status. Iron is distributed differently in central nervous system in male and female rats. However, the precise mechanisms need further study.

  6. Cognitive functioning of the aging brain

    OpenAIRE

    Tam, Man-kin, Helena; 譚敏堅

    2013-01-01

    This thesis contains two studies which examined the cognitive functioning of the aging brain. Specifically, age-related changes in processing speed and its remediation via cognitive training were studied. In study 1, younger adults (n = 34) and older adults (n = 39) were recruited to investigate the age-related differences in the relationships between processing speed and general cognitive status (GCS). Their performance in GCS (as measured by The Montreal Cognitive Assessment, Hong Kong Vers...

  7. High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging.

    Science.gov (United States)

    Harris, Janna L; Yeh, Hung-Wen; Swerdlow, Russell H; Choi, In-Young; Lee, Phil; Brooks, William M

    2014-07-01

    Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging.

  8. Susceptibility to calcium dysregulation during brain aging

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2009-11-01

    Full Text Available Calcium (Ca2+ is a highly versatile intracellular signaling molecule that is essential for regulating a variety of cellular and physiological processes ranging from fertilization to programmed cell death. Research has provided ample evidence that brain aging is associated with altered Ca2+ homeostasis. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review takes a broader perspective, assessing age-related changes in Ca2+ sources, Ca2+ sequestration, and Ca2+ binding proteins throughout the nervous system. The nature of altered Ca2+ homeostasis is cell specific and may represent a deficit or a compensatory mechanism, producing complex patterns of impaired cellular function. Incorporating the knowledge of the complexity of age-related alterations in Ca2+ homeostasis will positively shape the development of highly effective therapeutics to treat brain disorders.

  9. Light-sensitive brain pathways and aging.

    Science.gov (United States)

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  10. Neuroglobin in the rat brain: localization

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Allen, Gregg C; Nyengaard, Jens Randel

    2008-01-01

    in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation...

  11. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats.

  12. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain Efectos moduladores de la N-acetilcisteína sobre la corteza cerebral y las regiones cerebelosas sobre la del cerebro senescente de rata

    Directory of Open Access Journals (Sweden)

    S. Singh Kanwar

    2007-02-01

    Full Text Available Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since Nacetylcysteine (NAC has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH content along with the activities of superoxide dismutase (SOD and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months and older (14 months female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day, lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older rats. Further, in the younger rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.El estrés oxidativo se ha implicado en el envejecimiento cerebral y en los trastornos neurodegenerativos asociados con la edad. Puesto que recientemente se ha demostrado que la N-acetilcisteína (NAC previene el daño oxidativo en el cerebro senescente, hemos explorado los efectos de este antioxidante tiólico sobre

  13. Functional interrelationship of brain aging and delirium.

    Science.gov (United States)

    Rapazzini, Piero

    2016-02-01

    Theories on the development of delirium are complementary rather than competing and they may relate to each other. Here, we highlight that similar alterations in functional brain connectivity underlie both the observed age-related deficits and episodes of delirium. The default mode network (DMN) is a group of brain regions showing a greater level of activity at rest than during attention-based tasks. These regions include the posteromedial-anteromedial cortices and temporoparietal junctions. Evidence suggests that awareness is subserved through higher order neurons associated with the DMN. By using functional MRI disruption of DMN, connectivity and weaker task-induced deactivations of these regions are observed both in age-related cognitive impairment and during episodes of delirium. We can assume that an acute up-regulation of inhibitory tone within the brain acts to further disrupt network connectivity in vulnerable patients, who are predisposed by a reduced baseline connectivity, and triggers the delirium.

  14. Brain plasticity, memory, and aging: a discussion

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, E.L.; Rosenzweig, M.R.

    1977-12-01

    It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing for the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.

  15. Two hands, one brain, and aging.

    Science.gov (United States)

    Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

    2017-02-08

    Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults.

  16. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    Science.gov (United States)

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

  17. Aquaporin 9 in rat brain after severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2012-03-01

    Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

  18. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio [Niigata Univ. (Japan). Brain Research Inst.

    2001-12-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

  19. Aging causes exacerbated ischemic brain injury and failure of sevoflurane post-conditioning: role of B-cell lymphoma-2.

    Science.gov (United States)

    Dong, P; Zhao, J; Zhang, Y; Dong, J; Zhang, L; Li, D; Li, L; Zhang, X; Yang, B; Lei, W

    2014-09-05

    Aging is associated with exacerbated brain injury after ischemic stroke. Herein, we explored the possible mechanisms underlying the age-associated exacerbated brain injury after ischemic stroke and determined whether therapeutic intervention with anesthetic post-conditioning would provide neuroprotection in aged rats. Male Fisher 344 rats (young, 4 months; aged, 24 months) underwent 2h of middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion, with or without sevoflurane post-conditioning for 15 min immediately at the onset of reperfusion. Compared with young rats, aged rats showed larger infarct size, worse neurological scores and more TUNEL-positive cells in the penumbral cerebral cortex at 24h after MCAO. However, edema formation and motor coordination were similar in both groups. Sevoflurane reduced the infarct size, edema formation, and TUNEL-positive cells, and improved the neurological outcome in young rats but not in aged rats. Molecular studies revealed that basal expression of the anti-apoptotic molecule B-cell lymphoma-2 (Bcl-2) in the brain was lower in aged rats compared with young rats before MCAO, while basal expression of the pro-apoptotic molecule Bcl-2-associated X protein (Bax) showed similar levels in both groups. MCAO reduced Bcl-2 expression and increased Bax expression in both groups; however, Bax increase was more pronounced in aged rats. In young rats, sevoflurane reversed the above MCAO-induced changes. In contrast, sevoflurane failed to enhance Bcl-2 expression but decreased Bax expression in aged rats. These findings suggest that aging-associated reduction in basal Bcl-2 expression in the brain contributes to increased neuronal injury by enhancing cell apoptosis after ischemic stroke. Sevoflurane post-conditioning failed to provide neuroprotection in aged rats, probably due to its inability to increase Bcl-2 levels and prevent apoptosis in the brain.

  20. Long-term visual object recognition memory in aged rats.

    Science.gov (United States)

    Platano, Daniela; Fattoretti, Patrizia; Balietti, Marta; Bertoni-Freddari, Carlo; Aicardi, Giorgio

    2008-04-01

    Aging is associated with memory impairments, but the neural bases of this process need to be clarified. To this end, behavioral protocols for memory testing may be applied to aged animals to compare memory performances with functional and structural characteristics of specific brain regions. Visual object recognition memory can be investigated in the rat using a behavioral task based on its spontaneous preference for exploring novel rather than familiar objects. We found that a behavioral task able to elicit long-term visual object recognition memory in adult Long-Evans rats failed in aged (25-27 months old) Wistar rats. Since no tasks effective in aged rats are reported in the literature, we changed the experimental conditions to improve consolidation processes to assess whether this form of memory can still be maintained for long term at this age: the learning trials were performed in a smaller box, identical to the home cage, and the inter-trial delays were shortened. We observed a reduction in anxiety in this box (as indicated by the lower number of fecal boli produced during habituation), and we developed a learning protocol able to elicit a visual object recognition memory that was maintained after 24 h in these aged rats. When we applied the same protocol to adult rats, we obtained similar results. This experimental approach can be useful to study functional and structural changes associated with age-related memory impairments, and may help to identify new behavioral strategies and molecular targets that can be addressed to ameliorate memory performances during aging.

  1. Microglia priming in the aging brain : Implications for neurodegeneration

    NARCIS (Netherlands)

    Darwin Arulseeli, Divya; Biber, Knut

    2016-01-01

    The primary aim of the thesis “Microglia priming in the aging brain: Implications for neurodegeneration” was to understand microglia phenotypes associated with brain aging and the potential mechanisms for this age-associated change. Microglia in the aging brain assume a hypersensitive proinflammator

  2. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions.

  3. Poststroke Cell Therapy of the Aged Brain

    Directory of Open Access Journals (Sweden)

    Aurel Popa-Wagner

    2015-01-01

    Full Text Available During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC, the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs, mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment.

  4. [Rat brain cells containing ezrin (cytovillin)].

    Science.gov (United States)

    Korzhevskiĭ, D E; Kirik, O V; Giliarov, A V

    2011-01-01

    Ezrin (cytovillin or p81 protein) is an actin-binding protein, a member of ERM (ezrin, radixin and moesin) family, which species contribute to stabilization of the plasma membrane-formed structures. The aim of the present study was to demonstrate the ezrin-containing cells in the rat brain and to describe their topography and morphological features. The most pronounced immunohistochemical reaction to ezrin was found in the epithelium of the choroid plexus, cells of the subcommissural organ and ventricular ependyma. Moreover, ezrin staining was also detected in the unidentifiable cells in the subventricular zone, rostral migration pathway and astrocytes in various brain areas. Preferential ezrin localization in the brain cells contributing to formation of barrier structures suggests its involvement in transport processes in the CNS.

  5. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging

    Directory of Open Access Journals (Sweden)

    Heather M Buechel

    2014-02-01

    Full Text Available Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/ stress hormone/ allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation, and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 mo. and aged (21 mo. male F344 rats into control and acute restraint (an animal model of psychosocial stress groups (n = 9-12/ group. We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the three hour restraint, as well as highly significant increases in blood glucocorticoid levels 21 hours after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  6. Aged rats are hypo-responsive to acute restraint: implications for psychosocial stress in aging.

    Science.gov (United States)

    Buechel, Heather M; Popovic, Jelena; Staggs, Kendra; Anderson, Katie L; Thibault, Olivier; Blalock, Eric M

    2014-01-01

    Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift in chronic psychosocial stress response, or the initial acute phase of that chronic response, have been less well-studied. Here, we separated young (3 month) and aged (21 month) male F344 rats into control and acute restraint (an animal model of psychosocial stress) groups (n = 9-12/group). We then assessed hippocampus-associated behavioral, electrophysiological, and transcriptional outcomes, as well as blood glucocorticoid and sleep architecture changes. Aged rats showed characteristic water maze, deep sleep, transcriptome, and synaptic sensitivity changes compared to young. Young and aged rats showed similar levels of distress during the 3 h restraint, as well as highly significant increases in blood glucocorticoid levels 21 h after restraint. However, young, but not aged, animals responded to stress exposure with water maze deficits, loss of deep sleep and hyperthermia. These results demonstrate that aged subjects are hypo-responsive to new-onset acute psychosocial stress, which may have negative consequences for long-term stress adaptation and suggest that age itself may act as a stressor occluding the influence of new onset stressors.

  7. “脑功复得”改善脑老化的基础研究%xperimental study on the effect of Naogongfude on the aging of the rat brain

    Institute of Scientific and Technical Information of China (English)

    何小川; 蔡文琴; 李泽桂; 杨忠

    2001-01-01

    Objective To evaluate the effect of Naogongfude (NGFD, a traditional Chinese medicine orally administrated) on learning and memory and the expressions of synaptophysin (SY) and Tau-protein in cerebral cortex and hippocampus in aged rats and to explore the possible mechanism. Methods Rats were divided into normal and neural disturbance groups according to the outcomes of active avoidance reaction (AAR) test, and then each group was randomly divided into control and NGFD-treated experimental groups. Animals were orally fed with NGFD for 2 months (5 ml/d) in experimental group or routinely fed in control and taken AAR and passive avoidance reaction (PAR) tests. After the rats were sacrificed, the synaptosome count, the expression of SY and Tau-protein, and the neuron apoptosis in cerebrum were examined. Results The rats after 2-month NGFD administration had an increased AAR acquisition, obviously delayed AAR extinction and prolonged step through latency (STL) of PAR. The number of synaptosomes was raised and the immunoreactive intensity of synaptophysin was increased remarkedly, while Tau-protein immunoreactivity and apoptotic cells were decreased in cerebrum. Conclusion NGFD does have the effect of improving brain function and putting off the aging of rat brain according to the results of behavior study and morphological observation.%目的 研究中药合剂 “脑功复得”口服液(以下简称脑功复得)对老龄大鼠学习记忆能力及大脑皮质海马突触泡膜素(Synaptophysin, SY)、Tau-蛋白表达等的影响,探讨其延缓脑老化的功效及可能机制。方法 应用爬杆主动回避反应(Active avoidance reaction,AAR)将动物分为学习记忆正常组和障碍组,再随机分别设置对照组(普食)和实验喂药组(5 ml/d,2月)。在此基础上进行AAR和多功能箱被动回避反应(Passive avoidance reaction,PAR)训练、突触体计数、突触泡膜素和Tau蛋白免疫组化染色

  8. The emotion paradox in the aging brain.

    Science.gov (United States)

    Mather, Mara

    2012-03-01

    This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults' ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults' avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, although age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences.

  9. Relationship between aged-rat brain fatty acid composition and fatty acid beta-oxidation%老年大鼠脑脂肪酸含量与脂肪酸β-氧化的关系

    Institute of Scientific and Technical Information of China (English)

    杨磊; 石如玲; 张煜; 赵春澎; 付云; 黄艳梅

    2011-01-01

    目的 比较老年及青年大鼠脑脂肪酸含量、肝脏脂肪酸β-氧化关键酶表达水平的不同,探讨衰老时脂肪酸含量的变化与脂肪酸β-氧化功能的关系.方法 老年组和青年组大鼠各10只,用气相色谱法分析脑皮质脂肪酸含量,用反转录聚合酶链反应(RT-PCR)方法测定过氧化物酶体β-氧化关键酶脂酰辅酶A氧化酶(AOX1)、线粒体β-氧化关键酶肉碱脂酰转移酶1( CPT1)及过氧化物酶体增殖剂激活受体α(PPARα) mRNA的表达水平,用游离脂肪酸试剂盒测定血清游离脂肪酸(FFA)含量.结果 与青年组相比,老年组大鼠脑内C18∶0、C20∶4、C22∶6含量降低(P<0.05或P<0.01),脑内C16∶1、C18∶1、C20∶0、C20∶1、C22∶1、C24∶0、C24∶1含量升高(P<0.05或P<0.01),肝脏AOX1、CPT1、PPARα mRNA水平降低(P<0.05),血清总FFA含量降低(P<0.05).结论 衰老时大鼠脑脂肪酸含量变化的原因可能由线粒体和过氧化物酶体β-氧化功能降低所致.%Objective To analyze the differences of brain fatty acid content and liver fatty acid beta-oxidation enzyme expression between aged and young rats, and to explore the relationship between aged brain fatty acid composition and fatty acid beta-oxidation. Methods Old (22 months) and young (3 months) male rats were used in this experiment. Every ten mice in old group and young group. Fatty acid composition and contents of cerebral cortex were detected by gas chromatography analysis. The mRNA levels of acyl-CoA oxidase 1 (AOX1) ,camitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-ac-tivated receptor-a (PPARa) in liver were detected by reverse transcription-polymerase chain reaction (RT-PCR). Serum free fatty acid (FFA) level was measured by the assay kit. Results Compared with the young group, C18 : 0.C20 : 4 and C22 : 6 levels decreased( P<0.05 or P<0.01), while C16 : 1.C18 : l,C20 :0,C20 : 1,C22 : 1,C24 : 0 and C24 : 1 levels increased (P< 0.05 orP<0

  10. Increased brain-predicted aging in treated HIV disease

    Science.gov (United States)

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  11. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity.

  12. Studies of aluminum in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

    1985-01-01

    The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

  13. Age-dependent effect of static magnetic field on brain tissue hydration.

    Science.gov (United States)

    Deghoyan, Anush; Nikoghosyan, Anna; Heqimyan, Armenuhi; Ayrapetyan, Sinerik

    2014-01-01

    Age-dependent effect of Static Magnetic Field (SMF) on rats in a condition of active and inactive Na(+)/K(+) pump was studied for comparison of brain tissues hydration state changes and magnetic sensitivity. Influence of 15 min 0, 2 Tesla (T) SMF on brain tissue hydration of three aged groups of male albino rats was studied. Tyrode's physiological solution and 10(-4) M ouabain was used for intraperitoneal injections. For animal immobilization, the liquid nitrogen was used and the definition of tissue water content was performed by tissue drying method. Initial water content in brain tissues of young animals is significantly higher than in those of adult and aged ones. SMF exposure leads to decrease of water content in brain tissues of young animals and increase in brain tissues of adult and aged ones. In case of ouabain-poisoned animals, SMF gives reversal effects on brain tissue's hydration both in young and aged animals, while no significant effect on adults is observed. It is suggested that initial state of tissue hydration could play a crucial role in animal age-dependent magnetic sensitivity and the main reason for this could be age-dependent dysfunction of Na(+)/K(+) pump.

  14. Grape powder treatment prevents anxiety-like behavior in a rat model of aging.

    Science.gov (United States)

    Patki, Gaurav; Ali, Quaisar; Pokkunuri, Indira; Asghar, Mohammad; Salim, Samina

    2015-06-01

    Earlier, we have reported that grape powder (GP) treatment prevented pharmacologic and psychological stress-induced anxiety-like behavior and memory impairment in rats. Protective effects of GP were attributed to its antioxidant effects. In this study, we tested the hypothesis that age-associated behavioral and cognitive deficits such as anxiety and memory impairment will be ameliorated with GP treatment. Using a National Institute of Aging recommended rodent model of aging, we examined a potentially protective role of antioxidant-rich GP in age-associated anxiety-like behavior and memory impairment. Male Fischer 344 rats were randomly assigned into 4 groups: young rats (3 months old) provided with tap water or with 15 g/L GP dissolved in tap water for 3 weeks, aged rats (21 months old) provided with tap water or with GP-treated tap water for 3 weeks (AG-GP). Anxiety-like behavior was significantly greater in aged rats compared with young rats, GP-treated young rats, or aged control rats (P treatment prevented age-induced anxiety-like behavior in AG-GP rats (P treatment in AG-GP rats. Furthermore, aged rats showed increased level of physiological stress (corticosterone) and increased oxidative stress in the plasma (8-isoprostane) as well as in selected brain areas (protein carbonylation). Grape powder treatment prevented age-induced increase in corticosterone levels and plasma 8-isoprostane levels in aged rats (P anxiety-like behavior in rats, whereas age-associated memory deficits seem unaffected with GP treatment.

  15. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents

    OpenAIRE

    2013-01-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator...

  16. Age-related differences in the toxicity of ochratoxin A in female rats.

    Science.gov (United States)

    Dortant, P M; Peters-Volleberg, G W; Van Loveren, H; Marquardt, R R; Speijers, G J

    2001-01-01

    Ochratoxin A (OTA) is a mycotoxin found in food and feedstuffs of plant and animal origin. OTA exposure is related to nephropathy in humans. Age-related differences, especially in nephro- and immunotoxicity of OTA, were investigated in young adult (aged 12 weeks) and old (aged 27-30 months) female SPF Wag rats, treated by gavage with 0, 0.07, 0.34 or 1.68 mg OTA/kg body weight for 4 weeks. In both age groups, survival was significantly decreased in the highest dose group. Clinical condition, body weight, clinical chemistry parameters (ALAT, ASAT, creatinin and urea) and target organs (as identified by weight and pathology - kidney, liver, adrenals, forestomach and brain) were affected by age and dose, but often more severely in old than in young rats. OTA induced primarily nephropathy. Old rats were more sensitive to induction of tubular karyomegaly and vacuolation/necrosis. In young rats, OTA induced a dose-related thickening of the basement membrane and reduction in splenic T-cell fraction. Decreased IgG levels were seen at 0.34 mg/kg OTA (young and old rats) and 1.68 mg/kg OTA (young rats). Vacuolation of the white brain matter (cerebellar medulla and ventral parts of the brain stem) was significantly increased in young rats at 0.34 and 1.68 mg/kg OTA and in old rats at 0.07 and 0.34 mg/kg OTA. It was concluded that: (1) the profiles of OTA toxicity for both age groups are similar, with the kidney and possibly the brain being primary target organs; (2) based on clinical and pathological data old rats are more sensitive to OTA than young rats; and (3) the immune system is probably not the primary target of OTA toxicity.

  17. The quantitative analysis of S100 in the brain tissue and serum following diffuse brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Wang Qi; Huang Ping; Xing Bo; Tuo Ya; Zhang Yongpan; Tian Weiping; Wang Zhenyuan

    2007-01-01

    Objective To investigate the dynamics of the level of S100 in cerebrum, brainstem, and serum following the diffuse brain injury in rats and provide the experimental evidences for estimating injury time. Methods ELISA was used to determine whether S100 protein is changed after diffuse brain injury in rats. Forty rats were sacrificed at 0.5 hour, 2 hours, 4 hours, 12 hours, 24 hours, 3 d and 7 d after diffuse brain injury and normal rats as control. Results The level of S100 in cerebrum, brainstem, and serum increased, followed by a decrease, and then further increased. The level of S100 could be detected to increase at 30 minutes and reached the peak at 4 hours after DBI. The level decreased gradually to the normal at 1d and till 3 d formed the second peak. The level returned to the normal at 7d following injury again. In the postmortem injury groups, there were no significant changes compared to the control group. Conclusion The present study showed that the time-dependent expression of S100 is obvious following diffuse brain injury in rats and suggested that S100 will be a suitable marker for diffuse brain injury age determination.

  18. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

    Science.gov (United States)

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-07-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging.

  19. Exercise and the Aging Brain. (The 1982 C. H. McCloy Research Lecture)

    Science.gov (United States)

    Spirduso, Waneen W.

    1983-01-01

    Exercise may postpone the deterioration in response speed that generally appears in the motor system of the aging by maintaining the nigrostriatal dopaminergic system in the brain. Exercise may also ameliorate symptoms of Parkinson's disease. Results of laboratory studies involving animals and rats are reported. (Author/PP)

  20. Brain Aging in the Oldest-Old

    Directory of Open Access Journals (Sweden)

    A. von Gunten

    2010-01-01

    Full Text Available Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs and senile plaques (SPs as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions

  1. Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

    Science.gov (United States)

    Banks, William A; Abrass, Christine K; Hansen, Kim M

    2016-01-01

    Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments.

  2. Effects of neonatal treatment with the TRPV1 agonist, capsaicin, on adult rat brain and behaviour.

    Science.gov (United States)

    Newson, Penny N; van den Buuse, Maarten; Martin, Sally; Lynch-Frame, Ann; Chahl, Loris A

    2014-10-01

    Treatment of neonatal rats with the transient receptor potential vanilloid 1 (TRPV1) channel agonist, capsaicin, produces life-long loss of sensory neurons expressing TRPV1 channels. Previously it was shown that rats treated on day 2 of life with capsaicin had behavioural hyperactivity in a novel environment at 5-7 weeks of age and brain changes reminiscent of those found in subjects with schizophrenia. The objective of the present study was to investigate brain and behavioural responses of adult rats treated as neonates with capsaicin. It was found that the brain changes found at 5-7 weeks in rats treated as neonates with capsaicin persisted into adulthood (12 weeks) but were less in older rats (16-18 weeks). Increased prepulse inhibition (PPI) of acoustic startle was found in these rats at 8 and 12 weeks of age rather than the deficit commonly found in animal models of schizophrenia. Subjects with schizophrenia also have reduced flare responses to niacin and methylnicotinate proposed to be mediated by prostaglandin D2 (PGD2). Flare responses are accompanied by cutaneous plasma extravasation. It was found that the cutaneous plasma extravasation responses to methylnicotinate and PGD2 were reduced in capsaicin-treated rats. In conclusion, several neuroanatomical changes observed in capsaicin-treated rats, as well as the reduced cutaneous plasma extravasation responses, indicate that the role of TRPV1 channels in schizophrenia is worthy of investigation.

  3. Social support, stress and the aging brain.

    Science.gov (United States)

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress.

  4. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  5. Neuroethics in the Age of Brain Projects.

    Science.gov (United States)

    Greely, Henry T; Ramos, Khara M; Grady, Christine

    2016-11-02

    Neuroscience advances have brought important ethical questions. The recent launch of two large brain projects, the United States BRAIN Initiative and the European Union Human Brain Project, should accelerate progress in understanding the brain. This article examines neuroethics in those two projects, as well as its exploration by other efforts.

  6. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  7. Congenital viral infections of the brain: lessons learned from lymphocytic choriomeningitis virus in the neonatal rat.

    Directory of Open Access Journals (Sweden)

    Daniel J Bonthius

    2007-11-01

    Full Text Available The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region-virus-immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV

  8. Incentive relativity in middle aged rats.

    Science.gov (United States)

    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion.

  9. Want a Sharper Brain as You Age? Volunteer!

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162899.html Want a Sharper Brain as You Age? Volunteer! Study finds slight improvement in ... sharper mental skills at the age of 50, a new study suggests. British researchers said their findings ...

  10. Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Dezhi Kang; Zhang Guo

    2008-01-01

    BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats

  11. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  12. 26Al uptake and accumulation in the rat brain

    Science.gov (United States)

    Yumoto, S.; Nagai, H.; Imamura, M.; Matsuzaki, H.; Hayashi, K.; Masuda, A.; Kumazawa, H.; Ohashi, H.; Kobayashi, K.

    1997-03-01

    To investigate the cause of Alzheimer's disease (senile dementia), 26Al incorporation in the rat brain was studied by accelerator mass spectrometry (AMS). When 26Al was injected into healthy rats, a considerable amount of 26Al entered the brain (cerebrum) through the blood-brain barrier 5 days after a single injection, and the brain 26Al level remained almost constant from 5 to 270 days. On the other hand, the level of 26Al in the blood decreased remarkably 75 days after injection. Approximately 89% of the 26Al taken in by the brain cell nuclei bound to chromatin. This study supports the theory that Alzheimer's disease is caused by irreversible accumulation of aluminium (Al) in the brain, and brain cell nuclei.

  13. The beneficial effects of tree nuts on the aging brain

    Science.gov (United States)

    Dietary patterns may play an important role in protecting the brain from the cellular and cognitive dysfunction associated with the aging process and neurodegenerative diseases. Tree nuts are showing promise as possible dietary interventions for age-related brain dysfunction. Tree nuts are an impo...

  14. Stochastic fluctuations in gene expression in aging hippocampal neurons could be exacerbated by traumatic brain injury.

    Science.gov (United States)

    Shearer, Joseph; Boone, Deborah; Weisz, Harris; Jennings, Kristofer; Uchida, Tatsuo; Parsley, Margaret; DeWitt, Douglas; Prough, Donald; Hellmich, Helen

    2016-04-01

    Traumatic brain injury (TBI) is a risk factor for age-related dementia and development of neurodegenerative disorders such as Alzheimer's disease that are associated with cognitive decline. The exact mechanism for this risk is unknown but we hypothesized that TBI is exacerbating age-related changes in gene expression. Here, we present evidence in an animal model that experimental TBI increases age-related stochastic gene expression. We compared the variability in expression of several genes associated with cell survival or death, among three groups of laser capture microdissected hippocampal neurons from aging rat brains. TBI increased stochastic fluctuations in gene expression in both dying and surviving neurons compared to the naïve neurons. Increases in random, stochastic fluctuations in prosurvival or prodeath gene expression could potentially alter cell survival or cell death pathways in aging neurons after TBI which may lead to age-related cognitive decline.

  15. The effects of aging on dopaminergic neurotransmission: a microPET study of [11C]-raclopride binding in the aged rodent brain.

    Science.gov (United States)

    Hoekzema, E; Herance, R; Rojas, S; Pareto, D; Abad, S; Jiménez, X; Figueiras, F P; Popota, F; Ruiz, A; Torrent, È; Fernández-Soriano, F J; Rocha, M; Rovira, M; Víctor, V M; Gispert, J D

    2010-12-29

    Rodent models are frequently used in aging research to investigate biochemical age effects and aid in the development of therapies for pathological and non-pathological age-related degenerative processes. In order to validate the use of animal models in aging research and pave the way for longitudinal intervention-based animal studies, the consistency of cerebral aging processes across species needs to be evaluated. The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging. In this study, we aimed to assess whether similar age effects can be discerned in rat brains, using in vivo molecular imaging with the radioactive compound [(11)C]-raclopride. We observed a robust decline in striatal [(11)C]-raclopride uptake in the aged rats in comparison to the young control group, comprising a 41% decrement in striatal binding potential. In accordance with human studies, these results indicate that substantial reductions in D2R availability can be measured in the aged striatal complex. Our findings suggest that rat and human brains exhibit similar biochemical alterations with age in the striatal dopaminergic system, providing support for the pertinence of rodent models in aging research.

  16. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild;

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....

  17. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  18. Plasticity of the aging brain: new directions in cognitive neuroscience.

    Science.gov (United States)

    Gutchess, Angela

    2014-10-31

    Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span.

  19. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    Science.gov (United States)

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  20. Adaptation of brain functional and structural networks in aging.

    Science.gov (United States)

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  1. Adaptation of brain functional and structural networks in aging.

    Directory of Open Access Journals (Sweden)

    Annie Lee

    Full Text Available The human brain, especially the prefrontal cortex (PFC, is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI, and high angular resolution diffusion imaging (HARDI, and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  2. Do glutathione levels decline in aging human brain?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain.

  3. Waxholm Space atlas of the Sprague Dawley rat brain

    OpenAIRE

    Papp, Eszter A.; Trygve B. Leergaard; Calabrese, Evan; Johnson, G. Allan; Bjaalie, Jan G.

    2014-01-01

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in ...

  4. Ketogenic diets: an historical antiepileptic therapy with promising potentialities for the aging brain.

    Science.gov (United States)

    Balietti, Marta; Casoli, Tiziana; Di Stefano, Giuseppina; Giorgetti, Belinda; Aicardi, Giorgio; Fattoretti, Patrizia

    2010-07-01

    Ketogenic diets (KDs), successfully used in the therapy of paediatric epilepsy for nearly a century, have recently shown beneficial effects also in cancer, obesity, diabetes, GLUT 1 deficiencies, hypoxia-ischemia, traumatic brain injuries, and neurodegeneration. The latter achievement designates aged individuals as optimal recipients, but concerns derive from possible age-dependent differences in KDs effectiveness. Indeed, the main factors influencing ketone bodies utilization by the brain (blood levels, transport mechanisms, catabolic enzymes) undergo developmental changes, although several reports indicate that KDs maintain some efficacy during adulthood and even during advanced aging. Encouraging results obtained in patients affected by age-related neurodegenerative diseases have prompted new interest on KDs' effect on the aging brain, also considering the poor efficacy of therapies currently used. However, recent morphological evidence in synapses of late-adult rats indicates that KDs consequences may be even opposite in different brain regions, likely depending on neuronal vulnerability to age. Thus, further studies are needed to design KDs specifically indicated for single neurodegenerative diseases, and to ameliorate the balance between beneficial and adverse effects in aged subjects. Here we review clinical and experimental data on KDs treatments, focusing on their possible use during pathological aging. Proposed mechanisms of action are also reported and discussed.

  5. Nimodipine Effects on Cerebral Microvessels and Sciatic Nerve in Aging Rats

    NARCIS (Netherlands)

    de Jong, Giena; Jansen, Arthur; Horvath, E.; Gispen, W.H.; Luiten, P.G.M.

    1992-01-01

    At the ultrastructural level different anomalies of the cerebral microvasculature were encountered in the brains of aged rats. These aberrations can either be attributed to degeneration processes or to the perivascular deposition of, e.g., collagen fibrils and other, unidentified, proteinous debris.

  6. Actin purification from a gel of rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Peron-Renner, M; Coffe, G; Pudles, J

    1984-01-01

    Actin, 99% pure, has been recovered from rat brain with a high yield (greater than 15 mg/100 g brain). We have shown that: 1. a low ionic strength extract from rat brain tissue is capable of giving rise to a gel; 2. actin is the main gel component and its proportion is one order of magnitude higher than in the original extract; 3. actin can be isolated from this extract by a three-step procedure involving gelation, dissociation of the gel in 0.6 M KCl, followed by one or two depolymerization-polymerization cycles.

  7. Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

    Directory of Open Access Journals (Sweden)

    Brishna Soraya Kamal

    2013-09-01

    Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

  8. Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders.

    Science.gov (United States)

    Sibille, Etienne

    2013-03-01

    The increased risk for neurodegenerative and neuropsychiatric disorders associated with extended lifespan has long suggested mechanistic links between chronological age and brain-related disorders, including depression, Recent characterizations of age-dependent gene expression changes now show that aging of the human brain engages a specific set of biological pathways along a continuous lifelong trajectory, and that the same genes that are associated with normal brain aging are also frequently and similarly implicated in depression and other brain-related disorders. These correlative observations suggest a model of age-by-disease molecular interactions, in which brain aging promotes biological changes associated with diseases, and additional environmental factors and genetic variability contribute to defining disease risk or resiliency trajectories. Here we review the characteristic features of brain aging in terms of changes in gene function over time, and then focus on evidence supporting accelerated molecular aging in depression. This proposed age-by-disease biological interaction model addresses the current gap in research between "normal" brain aging and its connection to late-life diseases. The implications of this model are profound, as it provides an investigational framework for identifying critical moderating factors, outlines opportunities for early interventions or preventions, and may form the basis for a dimensional definition of diseases that goes beyond the current categorical system.

  9. The expression of Fetuin-A in brain tissues of WAG/Rij Rats, genetic rat model of absence epilepsy

    Directory of Open Access Journals (Sweden)

    Ramazan Yüksel

    2015-12-01

    Full Text Available Objective: In the present study, we aimed to determine the Fetuin-A levels in different regions of the brain in absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij rats in order to contribute the identification of new potential biomarkers of the diagnosis, prognosis and follow up the epilepsy treatment. Methods: 1, 3 and 6 months old male WAG/Rij rats (n=21 with absence epilepsy were used in this study. All of the rats were decapitated under anesthesia and their cortex and thalamus tissues were isolated. Fetuin-A levels of the groups were determined by Western Blot method by using standard techniques and differences between densities of the groups were compared. Results: According to data obtained, there was no Fetuin-A expression in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy. Conclusion: In this study, it was shown that Fetuin-A is not expressed in brain cortex and thalamus tissues of WAG/Rij rats with absence epilepsy throughout the age-related development. By evaluating the findings obtained, extensive researches that contain molecular and histological methods must be planned, Fetuin-A findings that are obtained experimentally must be confirmed. J Clin Exp Invest 2015; 6 (4: 387-390

  10. The Role of Brain Aging in Cognition and Motor Function

    NARCIS (Netherlands)

    Y.Y. Hoogendam (Jory)

    2014-01-01

    markdownabstract__Abstract__ Aging of the population is accompanied by many challenges, such as the maintenance of health and quality of life during older age. An important aspect of living longer is that old age is related to disease and loss of functions. The loss of brain functions poses a large

  11. Brain glucose content in fetuses of ethanol-fed rats

    Energy Technology Data Exchange (ETDEWEB)

    Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

    1986-03-01

    The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

  12. Accelerated Brain Aging in Schizophrenia : A Longitudinal Pattern Recognition Study

    NARCIS (Netherlands)

    Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  13. Accelerated brain aging in schizophrenia : A longitudinal pattern recognition study

    NARCIS (Netherlands)

    Schnack, Hugo G.; Van Haren, Neeltje E M; Nieuwenhuis, Mireille; Pol, Hilleke E Hulshoff; Cahn, Wiepke; Kahn, René S.

    2016-01-01

    OBJECTIVE: Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used

  14. Exploring age-related brain degeneration in meditation practitioners.

    Science.gov (United States)

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  15. Modeling the brain morphology distribution in the general aging population

    Science.gov (United States)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  16. Non-signalling energy use in the developing rat brain.

    Science.gov (United States)

    Engl, Elisabeth; Jolivet, Renaud; Hall, Catherine N; Attwell, David

    2017-03-01

    Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.

  17. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  18. Effect of Pomegranate Juice and Apple Juice on Free Radical Metabolism in Liver, Heart and Brain of Aged Rats%石榴汁和苹果汁干预对老龄大鼠肝、心、脑组织自由基代谢的影响

    Institute of Scientific and Technical Information of China (English)

    徐静; 刁焕荣; 拱玉华; 郭长江; 韦京豫; 杨继军

    2011-01-01

    Objective To study the effect of pomegranate juice and apple juice on free radical metabolism in the liver, heart and brain tissues of aged rats. Methods Thirty aged Wistar rats (22 months old) were randomly divided into three groups: pomegranate juice and apple juice as two experimental groups, while distilled water as normal control group. They were administrated fruit juices or distilled water respectively by gavage daily for 4 weeks. At the end of experiment, total antioxidant capacity (TAOC), content of MDA and free radical of the liver, heart and brain tissues were measured. Results The aged rats in pomegranate group showed significantly higher TAOC and lower content of free radicals in liver and brain respectively, while the concentrations of MDA in the liver, brain and heart tissues declined remarkably as compared to control group. The concentration of MDA and content of free radical in the liver tissue of aged rats in apple juice group decreased significantly. The pomegranate juice and apple juice had no evident effect on TAOC and concentration of free radical in the heart tissue of aged rats. Conclusion The pomegranate juice which showed stronger antioxidant capacity in vitro possessed higher capability to improve the metabolism offree radical in the liver, heart and brain tissues of aged rats.%目的 研究抗氧化活性较强的石榴汁和较弱的苹果汁对老龄大鼠肝、心、脑组织自由基代谢的影响.方法 自然衰老Wistar大鼠(22月龄)30只,随机分为三组,分别灌胃石榴汁3.2 ml,苹果汁2.4 ml和蒸馏水3.2 ml(对照组),实验周期4周,实验结束后取大鼠肝、心、脑组织制作匀浆液测定总抗氧化力、丙二醛(MDA)及自由基含量.结果 石榴汁干预组老龄大鼠肝脏、脑组织抗氧化能力显著升高、自由基水平明显下降,肝、心、脑MDA含量均显著降低,与对照组比较差异有统计学意义;苹果汁干预后老龄大鼠肝组织MDA含量及自由基水平明显

  19. Data for mitochondrial proteomic alterations in the aging mouse brain

    Directory of Open Access Journals (Sweden)

    Kelly L. Stauch

    2015-09-01

    Full Text Available Mitochondria are dynamic organelles critical for many cellular processes, including energy generation. Thus, mitochondrial dysfunction likely plays a role in the observed alterations in brain glucose metabolism during aging. Despite implications of mitochondrial alterations during brain aging, comprehensive quantitative proteomic studies remain limited. Therefore, to characterize the global age-associated mitochondrial proteomic changes in the brain, we analyzed mitochondria isolated from the brain of 5-, 12-, and 24-month old mice using quantitative mass spectrometry. We identified changes in the expression of proteins important for biological processes involved in the generation of precursor metabolites and energy through the breakdown of carbohydrates, lipids, and proteins. These results are significant because we identified age-associated proteomic changes suggestive of altered mitochondrial catabolic reactions during brain aging. The proteomic data described here can be found in the PRIDE Archive using the reference number PXD001370. A more comprehensive analysis of this data may be obtained from the article “Proteomic analysis and functional characterization of mouse brain mitochondria during aging reveal alterations in energy metabolism” in PROTEOMICS.

  20. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

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    Mohamed Naguib Zakaria

    2015-01-01

    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

  1. [Research of anti-aging mechanism of ginsenoside Rg1 on brain].

    Science.gov (United States)

    Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

    2014-11-01

    Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

  2. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    Directory of Open Access Journals (Sweden)

    Marta Karolina Zamroziewicz

    2016-06-01

    Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

  3. Emotion and aging: evidence from brain and behavior.

    Science.gov (United States)

    Ebner, Natalie C; Fischer, Håkan

    2014-01-01

    Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the 13 papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  4. Emotion and Aging: Evidence from Brain and Behavior

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2014-09-01

    Full Text Available Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging considering both brain and behavioral processes. The contributions featured in this issue adopt innovative theoretical perspectives and use novel methodological approaches to target a variety of topics that can be categorized into three overarching questions: How do cognition and emotion interact in aging in brain and behavior? What are behavioral and brain-related moderators of emotional aging? Does emotion-regulatory success as reflected in brain and behavior change with age? In this perspective paper we discuss theoretical innovation, methodological approach, and scientific advancement of the thirteen papers in the context of the broader literature on emotional aging. We conclude by reflecting on topics untouched and future directions to take.

  5. Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.

    Directory of Open Access Journals (Sweden)

    Diana M Sama

    Full Text Available The role of tumor necrosis factor α (TNF in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1 are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2 in aged (22 months but not young adult (6 months Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca(2+ channel (VSCC activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling.

  6. Do brain image databanks support understanding of normal ageing brain structure? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Dickie, David Alexander; Job, Dominic E.; Wardlaw, Joanna M. [University of Edinburgh, Division of Clinical Neurosciences, Western General Hospital, Brain Research Imaging Centre (BRIC), Edinburgh (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom); Poole, Ian [Toshiba Medical Visualisation Systems Europe, Ltd., Edinburgh (United Kingdom); Ahearn, Trevor S.; Staff, Roger T.; Murray, Alison D. [University of Aberdeen, Aberdeen Biomedical Imaging Centre, Aberdeen (United Kingdom); Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE), Edinburgh (United Kingdom)

    2012-07-15

    To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia. We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure. From nine eligible databanks, there appeared to be 944 normal subjects aged {>=}60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged {>=}60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data. Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. (orig.)

  7. Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice.

    Directory of Open Access Journals (Sweden)

    Ralph Timaru-Kast

    Full Text Available After traumatic brain injury (TBI elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months and old (21 months male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2% compared to young (0%. This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral

  8. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  9. Neuroglobin expression in rats after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Xin Lin; Min Li; Aijia Shang; Yazhuo Hu; Xiao Yang; Ling Ye; Suyan Bian; Zhongfeng Wang; Dingbiao Zhou

    2012-01-01

    In this study, we used a rat model of severe closed traumatic brain injury to explore the relationship between neuroglobin, brain injury and neuronal apoptosis. Real-time PCR showed that neuroglobin mRNA expression rapidly increased in the rat cerebral cortex, and peaked at 30 minutes and 48 hours following traumatic brain injury. Immunohistochemical staining demonstrated that neuroglobin expression increased and remained high 2 hours to 5 days following injury. The rate of increase in the apoptosis-related Bax/Bcl-2 ratio greatly decreased between 30 minutes and 1 hour as well as between 48 and 72 hours post injury. Expression of neuroglobin and the anti-apoptotic factor Bcl-2 greatly increased, while that of the proapoptotic factor decreased, in the cerebral cortex post severe closed traumatic brain injury. It suggests that neuroglobin might protect neurons from apoptosis after traumatic injury by regulating Bax/Bcl-2 pathway.

  10. Age-related alterations in behavioral and cerebral metabolic responses to the serotonin agonist meta-chlorophenylpiperazine in rats.

    Science.gov (United States)

    Freo, U; Rapoport, S I; Soncrant, T T

    1991-01-01

    To determine the functional relevance of the age-related neurochemical changes that occur in brain serotonin systems during aging, we measured the effects of the serotonin receptor agonist meta-chlorophenylpiperazine (MCPP) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) in awake rats. rCMRglc was determined in 74 regions of Fischer-344 rats aged 3, 12 and 24 months, at 15 and 90 min after MCPP 2.5 mg/kg IP, using the quantitative, autoradiographic [14C]2-deoxy-D-glucose technique. The time-course of motor performance following MCPP was assessed with a rotating rod. MCPP impaired motor performance in all ages maximally at 15-30 min. Three-month-old rats recovered completely within 60 min, whereas 12-month-old animals exhibited partial recovery and 24-month-old rats did not recover by 120 min. At 15 min after MCPP, rCMRglc was reduced in 51 of the 74 studied regions (overall decrease, 20%) of 3-month-old rats, in 21 regions (13% decrease) of 12-month-old rats and in 14 regions (2% decrease) of 24-month-old animals. Similar MCPP brain concentrations were achieved at 15 min in rats of all ages. The results suggest that the functional integrity of serotonergic transmission is reduced in aged rats and that the dysregulation is presynaptic.

  11. Aging of the Brain: How Can We Prevent It?

    Science.gov (United States)

    Jarvik, Lissy F.

    1988-01-01

    Contends distinction between normal and abnormal aging of the brain changes as data emerge which identify as pathology what had previously been considered the norm. Reviews research on effects of aging in twins begun in 1940s, focusing on facts related to intellectual decline, neuropsychological test performance relationship to dementia, and…

  12. A Brain Network Processing the Age of Faces

    NARCIS (Netherlands)

    Homola, G.A.; Jbabdi, S.; Beckmann, C.F.; Bartsch, A.J.

    2012-01-01

    Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previo

  13. Age-Related Deficits in Spatial Memory and Hippocampal Spines in Virgin, Female Fischer 344 Rats

    Directory of Open Access Journals (Sweden)

    Victoria N. Luine

    2011-01-01

    Full Text Available Effects of aging on memory and brain morphology were examined in aged, 21-month-old, and young, 4-month-old, Fischer 344 female rats. Spatial memory was assessed using the object placement task, and dendritic spine density was determined on pyramidal neurons in the hippocampus following Golgi impregnation. Consistent with previous studies, aged females showed poorer object placement performance than young subjects. Young subjects significantly discriminated the location of objects with a 1.5-hour intertrial delay while aged subjects did not. Spine density of basal dendrites on CA1 pyramidal cells was 16% lower in the aged subjects as compared to the young subjects. No differences in spine density were found between young and aged subjects in basal dendrites of CA1 or in either dendritic field of CA3 pyramidal neurons. Thus, decreased hippocampal CA1 dendritic spine density in aged rats may contribute to poorer spatial memory as compared to young rats. The possibility that the neuroplastic changes observed in this study may pertain only to female subjects having had a specific set of life experiences is discussed. Different factors, such as reproductive status, diet, and handling may contribute to neuroplasticity of the brain during aging; however, this view requires further examination.

  14. ShcC proteins: brain aging and beyond.

    Science.gov (United States)

    Sagi, Orli; Budovsky, Arie; Wolfson, Marina; Fraifeld, Vadim E

    2015-01-01

    To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.

  15. Hearing Impairment Is Associated with Smaller Brain Volume in Aging

    Science.gov (United States)

    Rigters, Stephanie C.; Bos, Daniel; Metselaar, Mick; Roshchupkin, Gennady V.; Baatenburg de Jong, Robert J.; Ikram, M. Arfan; Vernooij, Meike W.; Goedegebure, André

    2017-01-01

    Although recent studies show that age-related hearing impairment is associated with cerebral changes, data from a population perspective are still lacking. Therefore, we studied the relation between hearing impairment and brain volume in a large elderly cohort. From the population-based Rotterdam Study, 2,908 participants (mean age 65 years, 56% female) underwent a pure-tone audiogram to quantify hearing impairment. By performing MR imaging of the brain we quantified global and regional brain tissue volumes (total brain volume, gray matter volume, white matter (WM) volume, and lobe-specific volumes). We used multiple linear regression models, adjusting for age, sex, head size, time between hearing test and MR imaging, and relevant cognitive and cardiovascular covariates. Furthermore, we performed voxel-based morphometry to explore sub-regional differences. We found that a higher pure-tone threshold was associated with a smaller total brain volume [difference in standardized brain volume per decibel increase in hearing threshold in the age-sex adjusted model: -0.003 (95% confidence interval -0.004; -0.001)]. Specifically, WM volume was associated. Both associations were more pronounced in the lower frequencies. All associations were consistently present in all brain lobes in the lower frequencies and in most lobes in the higher frequencies, and were independent of cognitive function and cardiovascular risk factors. In voxel-based analyses we found associations of hearing impairment with smaller white volumes and some smaller and larger gray volumes, yet these were statistically non-significant. Our findings demonstrate that hearing impairment in elderly is related to smaller total brain volume, independent of cognition and cardiovascular risk factors. This mainly seems to be driven by smaller WM volume, throughout the brain.

  16. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    Science.gov (United States)

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  17. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  18. Distribution of nimodipine in brain following intranasal administration in rats

    Institute of Scientific and Technical Information of China (English)

    Qi-zhi ZHANG; Xin-guo JIANG; Chun-hua WU

    2004-01-01

    AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS:Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively.The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

  19. Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain.

    Science.gov (United States)

    Laitman, Benjamin M; John, Gareth R

    2015-01-01

    Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

  20. The rate of training response to aerobic exercise affects brain function of rats.

    Science.gov (United States)

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.

  1. Brain catecholamines in spontaneously hypertensive and DOCA-salt hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Fujino,Kazuyuki

    1984-08-01

    Full Text Available The concentrations and alpha-methyl-p-tyrosine (alpha-MPT induced disappearance of catecholamines, adrenaline, noradrenaline and dopamine, were measured in selected areas of the brainstem and hypothalamus of spontaneously hypertensive rats (SHR and deoxycorticosterone acetate (DOCA-salt hypertensive rats. The catecholamine levels were measured by a sensitive radioenzymatic assay method combined with microdissection of the rat brain. The adrenaline concentration was higher in the area A1 of young SHR, but not in adult SHR, than in age-matched control rats. Noradrenaline concentrations and the alpha-MPT induced noradrenaline disappearance were less in the rostral part of the nucleus tractus solitarii (NTS and the nucleus hypothalamic anterior of young SHR, and in the rostral part of the NTS of adult SHR. On the other hand in DOCA-salt hypertensive rats, the concentrations of adrenaline and noradrenaline were the same as in control rats in the examined areas. The alpha-MPT induced noradrenaline disappearance was less in the rostral part of the NTS of DOCA-salt hypertensive rats. Dopamine concentrations and the alpha-MPT induced dopamine disappearance were the same in the examined areas of SHR and DOCA-salt hypertensive rats. The results suggest that SHR have a change in adrenergic neural activity in the brainstem and a decrease in noradrenergic neural activity in the brainstem and hypothalamus while DOCA-salt hypertensive rats have a decrease in noradrenergic neural activity in the brainstem. Such changes in brain catecholaminergic neurons may have played an important role in the development of hypertension in these rats.

  2. Oxidative damage to rat brain in iron and copper overloads.

    Science.gov (United States)

    Musacco-Sebio, Rosario; Ferrarotti, Nidia; Saporito-Magriñá, Christian; Semprine, Jimena; Fuda, Julián; Torti, Horacio; Boveris, Alberto; Repetto, Marisa G

    2014-08-01

    This study reports on the acute brain toxicity of Fe and Cu in male Sprague-Dawley rats (200 g) that received 0 to 60 mg kg(-1) (ip) FeCl2 or CuSO4. Brain metal contents and time-responses were determined for rat survival, in situ brain chemiluminescence and phospholipid and protein oxidation products. Metal doses hyperbolically defined brain metal content. Rat survival was 91% and 60% after Fe and Cu overloads. Brain metal content increased from 35 to 114 μg of Fe per g and from 3.6 to 34 μg of Cu per g. Brain chemiluminescence (10 cps cm(-2)) increased 3 and 2 times after Fe and Cu overloads, with half maximal responses (C50) of 38 μg of Fe per g of brain and 15 μg of Cu per g of brain, and with half time responses (t1/2) of 12 h for Fe and 20 h for Cu. Phospholipid peroxidation increased by 56% and 31% with C50 of 40 μg of Fe per g and 20 μg of Cu per g and with t1/2 of 9 h and 14 h. Protein oxidation increased by 45% for Fe with a C50 of 40 μg of Fe per g and 18% for Cu with a C50 of 10 μg of Cu per g and a t1/2 of 12 h for both metals. Fe and Cu brain toxicities are likely mediated by Haber-Weiss type HO˙ formation with subsequent oxidative damage.

  3. Emotion and aging: evidence from brain and behavior

    OpenAIRE

    2014-01-01

    Emotions play a central role in every human life from the moment we are born until we die. They prepare the body for action, highlight what should be noticed and remembered, and guide decisions and actions. As emotions are central to daily functioning, it is important to understand how aging affects perception, memory, experience, as well as regulation of emotions. The Frontiers research topic Emotion and Aging: Evidence from Brain and Behavior takes a step into uncovering emotional aging con...

  4. Sympathetic neuroaxonal dystrophy in the aged rat pineal gland.

    Science.gov (United States)

    Schmidt, Robert E; Dorsey, Denise A; Parvin, Curtis A; Beaudet, Lucie N

    2006-10-01

    Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats showed loss of nerve terminals as well as the development of neuroaxonal dystrophy (NAD), an ultrastructurally distinctive distal axonopathy, far in excess of that in young control rats. Immunolocalization of tyrosine hydroxylase confirmed the age-related loss of normal noradrenergic innervation and development of NAD. NAD was more frequent in aged female rats compared to males and was particularly severe in aged female Sprague-Dawley rats compared to Fischer-344 rats. Pineal NGF content was significantly increased or unchanged in female and male aged Fischer-344 rats, respectively, compared to young controls. The rat pineal is a sensitive experimental model for the quantitative ultrastructural examination of age-related neuropathological changes in nerve terminals of postganglionic noradrenergic sympathetic axons, changes which may reflect similar changes in the diffusely distributed sympathetic innervation of other targeted endorgans.

  5. Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups.

    Science.gov (United States)

    Yazdani, Armin; Khoja, Zehra; Johnstone, Aaron; Dale, Laura; Rampakakis, Emmanouil; Wintermark, Pia

    2016-01-01

    Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

  6. Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain.

    Science.gov (United States)

    Loane, David J; Deighan, Brian F; Clarke, Rachael M; Griffin, Rebecca J; Lynch, Aileen M; Lynch, Marina A

    2009-06-01

    Increased expression of proinflammatory cytokines, like interleukin-1 beta (IL-1 beta), is a feature of the aged brain and it is generally accepted that the primary cell source of these cytokines is activated microglia. In hippocampus of aged rats, the increase in IL-1 beta is accompanied by microglial activation and impaired long-term potentiation (LTP). Peroxisome proliferator-activated receptors (PPARs) possess anti-inflammatory properties that target microglia. In this study the PPAR gamma agonist, rosiglitazone, was orally administered to young and aged rats, and we report that the age-related increases in NO and IL-1 beta production were attenuated in hippocampus of rosiglitazone-treated aged rats and that this was associated with a restoration of LTP. In addition, treatment with rosiglitazone increased interleukin-4 (IL-4) mRNA and reversed the age-related decrease in hippocampal IL-4 concentration. Significantly, while rosiglitazone attenuated the LPS-induced increase in MHCII and IL-1 beta concentration in glia prepared from wildtype mice, it failed to exert an effect in glia prepared from IL-4(-/-) mice, thereby suggesting that the anti-inflammatory actions of rosiglitazone are mediated by its ability to increase IL-4 expression.

  7. Demonstration of endogenous imipramine like material in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Rehavi, M.; Ventura, I.; Sarne, Y.

    1985-02-18

    The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits (/sup 3/H) imipramine specific binding and mimics the inhibitory effect of imipramine on (/sup 3/H) serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits (/sup 3/H) imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum.

  8. Berry Fruit Supplementation in the Aging Brain

    Science.gov (United States)

    The onset of age-related neurodegenerative diseases such as Alzheimer’s or Parkinson’s Disease, superimposed on a declining nervous system, could exacerbate the motor and cognitive behavioral deficits that normally occur in senescence. In cases of severe deficits in memory or motor function, hospit...

  9. Attenuated inflammatory response in aged mice brains following stroke.

    Directory of Open Access Journals (Sweden)

    Matthias W Sieber

    Full Text Available BACKGROUND: Increased age is a major risk factor for stroke incidence, post-ischemic mortality, and severe and long-term disability. Stroke outcome is considerably influenced by post-ischemic mechanisms. We hypothesized that the inflammatory response following an ischemic injury is altered in aged organisms. METHODS AND RESULTS: To that end, we analyzed the expression pattern of pro-inflammatory cytokines (TNF, IL-1α, IL-1β, IL-6, anti-inflammatory cytokines (IL-10, TGFβ1, and chemokines (Mip-1α, MCP-1, RANTES of adult (2 months and aged (24 months mice brains at different reperfusion times (6 h, 12 h, 24 h, 2 d, 7 d following transient occlusion of the middle cerebral artery. The infarct size was assessed to monitor possible consequences of an altered inflammatory response in aged mice. Our data revealed an increased neuro-inflammation with age. Above all, we found profound age-related alterations in the reaction to stroke. The response of pro-inflammatory cytokines (TNF, and IL-1β and the level of chemokines (Mip-1α, and MCP-1 were strongly diminished in the aged post-ischemic brain tissue. IL-6 showed the strongest age-dependent decrease in its post-ischemic expression profile. Anti-inflammatory cytokines (TGFβ1, and IL-10 revealed no significant age dependency after ischemia. Aged mice brains tend to develop smaller infarcts. CONCLUSION: The attenuated inflammatory response to stroke in aged animals may contribute to their smaller infarcts. The results presented here highlight the importance of using aged animals to investigate age-associated diseases like stroke, and should be considered as a major prerequisite in the development of age-adjusted therapeutic interventions.

  10. The effect of chemotherapy on rat brain PET: preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Su; Kim, Il Han; Yu, A Ram; Park, Ji Ae; Woo, Sang Keun; Kim, Jong Guk; Cheon, Gi Jeong; Kim, Byeong Il; Choi, Chang Woon; Lim, Sang Moo; Kim, Hee Joung; Kim, Kyeong Min [Korea Institute Radiological and Medical Science, Seoul (Korea, Republic of)

    2010-10-15

    Chemotherapy was widely used for the therapy of cancer patients. When chemotherapy was performed, transient cognitive memory problem was occurred. This cognitive problem in brain was called as chemobrain. In this study, we have developed rat model for chemobrain. Cerebral glucose metabolism after chemotherapy was assessed using animal PET and voxel based statistical analysis method

  11. Effects of magnesium sulfate on traumatic brain edema in rats

    Institute of Scientific and Technical Information of China (English)

    冯东福; 朱志安; 卢亦成

    2004-01-01

    Objective: To investigate the effects of magnesium sulfate on traumatic brain edema and explore its possible mechanism.Methods: Forty-eight Sprague-Dawley ( SD ) rats were randomly divided into three groups: Control, Trauma and Treatment groups. In Treatment group, magnesium sulfate was intraperitoneally administered immediately after the induction of brain trauma. At 24 h after trauma, total tissue water content and Na + , K + , Ca2 + , Mg2+ contents were measured. Permeability of blood-brain barrier (BBB)was assessed quantitatively by Evans Blue (EB) dye technique. The pathological changes were also studied.Results: Water, Na + , Ca2 + and EB contents in Treatment group were significantly lower than those in Trauma group ( P < 0. 05 ). Results of light microscopy and electron microscopy confirmed that magnesium sulfate can attenuate traumatic brain injury and relieve BBB injury.Conclusions: Treatment with MgSO4 in the early stage can attenuate traumatic brain edema and prevent BBB injury.

  12. Brain tumors induced in rats by human adenovirus type 12

    Directory of Open Access Journals (Sweden)

    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  13. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats

    Directory of Open Access Journals (Sweden)

    Khairunnuur Fairuz Azman

    2016-01-01

    Full Text Available Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A, 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system.

  14. Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

    Science.gov (United States)

    Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J

    2014-12-01

    Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.

  15. In vivo calcium imaging of the aging and diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)

    2008-03-15

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  16. Inducible gene manipulations in brain serotonergic neurons of transgenic rats.

    Directory of Open Access Journals (Sweden)

    Tillmann Weber

    Full Text Available The serotonergic (5-HT system has been implicated in various physiological processes and neuropsychiatric disorders, but in many aspects its role in normal and pathologic brain function is still unclear. One reason for this might be the lack of appropriate animal models which can address the complexity of physiological and pathophysiological 5-HT functioning. In this respect, rats offer many advantages over mice as they have been the animal of choice for sophisticated neurophysiological and behavioral studies. However, only recently technologies for the targeted and tissue specific modification of rat genes - a prerequisite for a detailed study of the 5-HT system - have been successfully developed. Here, we describe a rat transgenic system for inducible gene manipulations in 5-HT neurons. We generated a Cre driver line consisting of a tamoxifen-inducible CreERT2 recombinase under the control of mouse Tph2 regulatory sequences. Tissue-specific serotonergic Cre recombinase expression was detected in four transgenic TPH2-CreERT2 rat founder lines. For functional analysis of Cre-mediated recombination, we used a rat Cre reporter line (CAG-loxP.EGFP, in which EGFP is expressed after Cre-mediated removal of a loxP-flanked lacZ STOP cassette. We show an in-depth characterisation of this rat Cre reporter line and demonstrate its applicability for monitoring Cre-mediated recombination in all major neuronal subpopulations of the rat brain. Upon tamoxifen induction, double transgenic TPH2-CreERT2/CAG-loxP.EGFP rats show selective and efficient EGFP expression in 5-HT neurons. Without tamoxifen administration, EGFP is only expressed in few 5-HT neurons which confirms minimal background recombination. This 5-HT neuron specific CreERT2 line allows Cre-mediated, inducible gene deletion or gene overexpression in transgenic rats which provides new opportunities to decipher the complex functions of the mammalian serotonergic system.

  17. Differential effects of exercise intensities in hippocampal BDNF, inflammatory cytokines and cell proliferation in rats during the postnatal brain development.

    Science.gov (United States)

    de Almeida, Alexandre Aparecido; Gomes da Silva, Sérgio; Fernandes, Jansen; Peixinho-Pena, Luiz Fernando; Scorza, Fulvio Alexandre; Cavalheiro, Esper Abrão; Arida, Ricardo Mario

    2013-10-11

    It has been established that low intensities of exercise produce beneficial effects for the brain, while high intensities can cause some neuronal damage (e.g. exacerbated inflammatory response and cell death). Although these effects are documented in the mature brain, the influence of exercise intensities in the developing brain has been poorly explored. To investigate the impact of exercise intensity in developing rats, we evaluated the hippocampal level of brain derived neurotrophic factor (BDNF), inflammatory cytokines (TNFα, IL6 and IL10) and the occurrence of hippocampal cell degeneration and proliferation at different stages of postnatal brain development of rats submitted to two physical exercise intensities. To this point, male rats were divided into different age groups: P21, P31, P41 and P51. Each age group was submitted to two exercise intensities (low and high) on a treadmill over 10 consecutive days, except the control rats. We verified that the density of proliferating cells was significantly higher in the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30 compared with high-intensity exercise and control rats. A significant increase of proliferative cell density was found in rats submitted to high-intensity exercise from P31 to P40 when compared to low-intensity exercise and control rats. Elevated hippocampal levels of IL6 were detected in rats submitted to high-intensity exercise from P21 to P30 compared to control rats. From P41 to P50 period, higher levels of BDNF, TNFα and IL10 were found in the hippocampal formation of rats submitted to high-intensity exercise in relation to their control rats. Our data show that exercise-induced neuroplastic effects on BDNF levels and cellular proliferation in the hippocampal region are dependent on exercise intensity and developmental period. Thus, exercise intensity is an inflammation-inducing factor and exercise-induced inflammatory response during the postnatal brain development is

  18. A brain network processing the age of faces.

    Directory of Open Access Journals (Sweden)

    György A Homola

    Full Text Available Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships.

  19. Brain energy metabolism and blood flow differences in healthy aging

    DEFF Research Database (Denmark)

    Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

    2012-01-01

    Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors...... find decreases of both CBF and CMRO(2) but increased OEF, while others find no change, and yet other find divergent changes. In this reanalysis of previously published results from positron emission tomography of healthy volunteers, we determined CMRO(2) and CBF in 66 healthy volunteers aged 21 to 81......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

  20. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  1. Changes of monoamine nervous transmitter and free radical met abolism in aged rats with gastrointestinal injury after brain ischemia reper fusion%脑缺血再灌注胃肠损伤老龄大鼠单胺类神经递质 和自由基代谢的变化

    Institute of Scientific and Technical Information of China (English)

    李建生; 赵君玫; 郭盛典; 李建国

    2001-01-01

    Objective: To study the mechanism of gastrointestinal injury after brain ischemia reperfusi on in aged rats from the changes of dopamine(DA),noradrenalin(NE),epinephrine(E) and the injury of free radical.Methods:Young(5months) and aged (20 months or more) rats were divided into young model group (YMG),young control group(YCG),aged model group (AMG),aged control group(ACG).The following items were measured in rats with 60 minute reperfusion after 30 minute brain ischemia:the pathological change of ga strointestinal tract:the activities of super-oxide dismutase(SOD),the contents of MDA,DA,NE,E. Results:The pathological change of gastrointestinal tract was found in the YMG and the AMG.The excitability of sympathetic-adrenal system was enhanced in the YMG and the AMG,this change in the AMG was serious compared w ith that in the YMG.The gastrointestinal MDA/SOD ratio was larger in the ACG and the YMG than that in the YCG.The stomach MDA/SOD ratio was larger in the AMG th an that in the ACG and the YMG.Conclusion: The gastrointestinal injury after brain ischemia rep erfusion in aged rats was correlated with the change of the enhanced excitabilit y of sympathetic-adrenal system and free radical injury.With aging these pathol ogical change were obvious and distinctive compared with that in the young rats.%目的:从多巴胺(DA)、去甲肾上腺素(NE)、肾上腺素(E)变化和自由基损伤方面揭示脑缺血再灌注胃肠损伤的机制。方法:青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组,观察大鼠全脑缺血30 min再灌注60 min后胃肠损伤的病理改变和超氧化物岐化酶(SOD)的活性及丙二醛(MDA)、DA、NE、E含量。结果:青年和老龄模型组胃肠出现明显的病理改变。青年和老龄模型组交感-肾上腺系统兴奋性增强,其中老龄模型组较青年模型组大鼠严重。老龄对照组和青年模型组胃肠组织MDA/SOD比值高于青年对照组,

  2. Enhanced post-ischemic neurogenesis in aging rats

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    Yao-Fang Tan

    2010-08-01

    Full Text Available Hippocampal neurogenesis persists in adult mammals, but its rate declines dramatically with age. Evidence indicates that experimentally-reduced levels of neurogenesis (e.g. by irradiation in young rats has profound influence on cognition as determined by learning and memory tests. In the present study we asked whether in middle-aged, 10-13 months old rats, cell production can be restored towards the level present in young rats. To manipulate neurogenesis we induced bilateral carotid occlusion with hypotension. This procedure is known to increase neurogenesis in young rats, presumably in a compensatory manner, but until now, has never been tested in aging rats. Cell production was measured at 10, 35 and 90 days after ischemia. The results indicate that neuronal proliferation and differentiation can be transiently restored in middle-aged rats. Furthermore, the effects are more pronounced in the dorsal as opposed to ventral hippocampus thus restoring the dorso-ventral gradient seen in younger rats. Our results support previous findings showing that some of the essential features of the age-dependent decline in neurogenesis are reversible. Thus, it may be possible to manipulate neurogenesis and improve learning and memory in old age.

  3. Life and death of neurons in the aging brain

    Science.gov (United States)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  4. Evolution of the aging brain transcriptome and synaptic regulation.

    Directory of Open Access Journals (Sweden)

    Patrick M Loerch

    Full Text Available Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4. However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.

  5. Long-term sequelae of perinatal asphyxia in the aging rat

    DEFF Research Database (Denmark)

    Weitzdoerfer, R; Gerstl, N; Hoeger, H;

    2002-01-01

    Information on the consequences of perinatal asphyxia (PA) on brain morphology and function in the aging rat is missing although several groups have hypothesized that PA may be responsible for neurological and psychiatric deficits in the adult. We therefore decided to study the effects of PA...... on the central nervous system (CNS) in terms of morphology, immunohistochemistry, neurology and behavior in the aging animal. Hippocampus and cerebellum were evaluated morphologically by histological, immunohistochemical and magnetic resonance imaging and cerebellum also by stereological tests. Neurological...... for understanding CNS pathology in the aging subject, animal or human....

  6. Manifold learning on brain functional networks in aging.

    Science.gov (United States)

    Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K

    2015-02-01

    We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan.

  7. DNA Strand Breaks, Neurodegeneration and Aging in the Brain

    Science.gov (United States)

    Katyal, Sachin; McKinnon, Peter J.

    2013-01-01

    Defective responses to DNA single- or double-strand breaks can result in neurological disease, underscoring the critical importance of DNA repair for neural homeostasis. Human DNA repair-deficient syndromes are generally congenital, in which brain pathology reflects the consequences of developmentally incurred DNA damage. Although, it is unclear to what degree DNA strand-break repair defects in mature neural cells contributes to disease pathology. However, DNA single-strand breaks are a relatively common lesion which if not repaired can impact cells via interference with transcription. Thus, this lesion, and probably to a lesser extent DNA double strand breaks, may be particularly relevant to aging in the neural cell population. In this review we will examine the consequences of defective DNA strand break repair towards homeostasis in the brain. Further, we also consider the utility of mouse models as reagents to understand the connection between DNA strand breaks and aging in the brain. PMID:18455751

  8. Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats.

    Science.gov (United States)

    Thangthaeng, Nopporn; Miller, Marshall G; Gomes, Stacey M; Shukitt-Hale, Barbara

    2015-12-01

    Decline in brain function during normal aging is partly due to the long-term effects of oxidative stress and inflammation. Several fruits and vegetables have been shown to possess antioxidant and anti-inflammatory properties. The present study investigated the effects of dietary mushroom intervention on mobility and memory in aged Fischer 344 rats. We hypothesized that daily supplementation of mushroom would have beneficial effects on behavioral outcomes in a dose-dependent manner. Rats were randomly assigned to receive a diet containing either 0%, 0.5%, 1%, 2%, or 5% lyophilized white button mushroom (Agaricus bisporus); after 8 weeks on the diet, a battery of behavioral tasks was given to assess balance, coordination, and cognition. Rats on the 2% or 5% mushroom-supplemented diet consumed more food, without gaining weight, than rats in the other diet groups. Rats in the 0.5% and 1% group stayed on a narrow beam longer, indicating an improvement in balance. Only rats on the 0.5% mushroom diet showed improved performance in a working memory version of the Morris water maze. When taken together, the most effective mushroom dose that produced improvements in both balance and working memory was 0.5%, equivalent to about 1.5 ounces of fresh mushrooms for humans. Therefore, the results suggest that the inclusion of mushroom in the daily diet may have beneficial effects on age-related deficits in cognitive and motor function.

  9. Alpha oscillatory correlates of motor inhibition in the aged brain

    Directory of Open Access Journals (Sweden)

    Marlene eBoenstrup

    2015-10-01

    Full Text Available Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time - early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains.

  10. New progress in brain aging and its related neurological diseases

    Directory of Open Access Journals (Sweden)

    Ming-wei ZHU

    2014-03-01

    Full Text Available Brain aging-related neurological diseases including Alzheimer's disease (AD, Parkinson's disease (PD and cerebral amyloid angiopathy (CAA have become one of the major diseases endangering the health of old people in China. Although the mechanism of brain aging and pathogenesis of its related neurodegenerative diseases remain unclear, protein pathological studies such as tau, α-synuclein (α-Syn, TDP-43 and amyloid-β protein (Aβ based on brain tissue bank and case registration database are opening the door to solve the mystery in the brain aging process and unlock pathogenesis of aging-related neurodegenerative diseases. Research on functional neuroimaging including 11C-PIB PET and 18F-FDDNP PET in Alzheimer's disease and 18F-FDG PET in Parkinson's disease, and biomarkers such as total-tau, phosphorylated-tau, and the 42 amino acid fragment of β-amyloid in cerebrospinal fluid (CSF in the preclinical stages of Alzheimer's disease now become hot topics in the field of elderly dementia and movement disorders. Clinicopathological correlation research of Alzheimer's disease, Parkinson's disease and cerebral amyloid angiopathy is also one of focuses in the geriatric neurological diseases. doi: 10.3969/j.issn.1672-6731.2014.03.004

  11. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    Science.gov (United States)

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  12. Effect of acute thioacetamide administration on rat brain phospholipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Osada, J.; Aylagas, H.; Miro-Obradors, M.J.; Arce, C.; Palacios-Alaiz, E.; Cascales, M. (Tufs Univ., Boston, MA (USA))

    1990-09-01

    Brain phospholipid composition and the ({sup 32}P)orthophosphate incorporation into brain phospholipids of control and rats treated for 3 days with thioacetamide were studied. Brain phospholipid content, phosphatidylcholine, phosphatidylethanolamine, lysolecithin and phosphatidic acid did not show any significant change by the effect of thioacetamide. In contrast, thioacetamide induced a significant decrease in the levels of phosphatidylserine, sphingomyelin, phosphatidylinositol and diphosphatidylglycerol. After 75 minutes of intraperitoneal label injection, specific radioactivity of all the above phospholipids with the exception of phosphatidylethanolamine and phosphatidylcholine significantly increased. After 13 hours of isotope administration the specific radioactivity of almost all studied phospholipid classes was elevated, except for phosphatidic acid, the specific radioactivity of which did not change and for diphosphatidylglycerol which showed a decrease in specific radioactivity. These results suggest that under thioacetamide treatment brain phospholipids undergo metabolic transformations that may contribute to the hepatic encephalopathy induced by thioacetamide.

  13. Expression of neuropeptide Y in rat brain ischemia

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    Babović Siniša S.

    2013-01-01

    Full Text Available Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum - especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack.

  14. Nerve growth factor receptor molecules in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Taniuchi, M.; Schweitzer, J.B.; Johnson, E.M. Jr.

    1986-03-01

    The authors have developed a method to immunoprecipitate rat nerve growth factor (NGF) receptor proteins and have applied the method to detect NGF receptor molecules in the rat brain. Crosslinking /sup 125/I-labeled NGF to either PC12 cells or cultured rat sympathetic neurons yielded two radiolabeled molecules (90 kDa and 220 kDa) that were immunoprecipitated by monoclonal antibody 192-IgG. Further, 192-IgG precipitated two radiolabeled proteins, with the expected sizes (80 kDa and 210 kDa) of noncrosslinked NGF receptor components, from among numerous surface-iodinated PC12 cell proteins. These results demonstrate the specific immunoprecipitation of NGF receptor molecules by 192-IgG. They applied the /sup 125/I-NGF crosslinking and 192-IgG-mediated immunoprecipitation procedures to plasma membrane preparations of rat brain: NGF receptor molecules of the same molecular masses as the peripheral receptor components were consistently detected in all regions and in preparations from whole brains. Removal of the peripheral sympathetic innervation of the brain did not eliminate these NGF receptor proteins, indicating that the receptor is endogenous to central nervous system tissues. They also observed retrograde transport of /sup 125/I-labeled 192-IgG from the parietal cortex to the nucleus basalis and from the hippocampus to the nucleus of the diagonal band of Broca and the medial septal nucleus. These findings demonstrate the presence in brain of NGF receptor molecules indistinguishable from those of the peripheral nervous system.

  15. Toluene effects on Oxidative Stress in Brain regions of Young-adult, Middleage,and Senescent Brown Norway Rats

    Science.gov (United States)

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. The objective was to test whether oxidative stress plays a role in the adver...

  16. Expression of the 5-HT receptors in rat brain during memory consolidation.

    Science.gov (United States)

    Meneses, A; Manuel-Apolinar, L; Rocha, L; Castillo, E; Castillo, C

    2004-07-09

    Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using 3H 5-HT as ligand, 2 nM, specific activity 123 Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.

  17. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    Directory of Open Access Journals (Sweden)

    K. M. Rice

    2014-01-01

    Full Text Available Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging.

  18. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS).

  19. Growth hormone prevents neuronal loss in the aged rat hippocampus.

    Science.gov (United States)

    Azcoitia, Iñigo; Perez-Martin, Margarita; Salazar, Veronica; Castillo, Carmen; Ariznavarreta, Carmen; Garcia-Segura, Luis M; Tresguerres, Jesus A F

    2005-05-01

    Decline of growth hormone (GH) with aging is associated to memory and cognitive alterations. In this study, the number of neurons in the hilus of the dentate gyrus has been assessed in male and female Wistar rats at 3, 6, 12, 14, 18, 22 and 24 months of age, using the optical fractionator method. Male rats had more neurons than females at all the ages studied. Significant neuronal loss was observed in both sexes between 22 and 24 months of age. In a second experiment, 22 month-old male and female rats were treated for 10 weeks with 2 mg/kg/day of GH or saline. At 24 months of age, animals treated with GH had more neurons in the hilus than animals treated with saline. These findings indicate that GH is neuroprotective in old animals and that its administration may ameliorate neuronal alterations associated to aging.

  20. Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces

    Directory of Open Access Journals (Sweden)

    Strazielle Nathalie

    2008-03-01

    Full Text Available Abstract Background Prostaglandin E2 (PGE2 is involved in the regulation of synaptic activity and plasticity, and in brain maturation. It is also an important mediator of the central response to inflammatory challenges. The aim of this study was to evaluate the ability of the tissues forming the blood-brain interfaces to act as signal termination sites for PGE2 by metabolic inactivation. Methods The specific activity of 15-hydroxyprostaglandin dehydrogenase was measured in homogenates of microvessels, choroid plexuses and cerebral cortex isolated from postnatal and adult rat brain, and compared to the activity measured in peripheral organs which are established signal termination sites for prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were identified and quantified by HPLC coupled to radiochemical detection. Results The data confirmed the absence of metabolic activity in brain parenchyma, and showed that no detectable activity was associated with brain microvessels forming the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase activity was measured in both fourth and lateral ventricle choroid plexuses from 2-day-old rats, albeit at a lower level than in lung or kidney. The activity was barely detectable in adult choroidal tissue. Metabolic profiles indicated that isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14-dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in the tissue rather than in the external medium, suggesting its release in the choroidal stroma. Conclusion The rat choroidal tissue has a significant ability to metabolize PGE2 during early postnatal life. This metabolic activity may participate in signal termination of centrally released PGE2 in the brain, or function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF during the critical early postnatal period of brain development.

  1. Aging and Gene Expression in the Primate Brain

    Energy Technology Data Exchange (ETDEWEB)

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

    It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes in the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.

  2. Huayu capsule enhances limb-catching capability of rats with experimental open traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Chunyang Zhou; Juan Zhang; Yong Wang; Haibing Qian; Li Gong; Guojun Huang

    2007-01-01

    BACKGROUND: It is hard to cure the open traumatic brain injury (TBI), especially for the brain functional recovery after brain injury. In this regard, traditional Chinese medicine (TCM) has a wide prospect.OBJECTIVE: To observe the effect of Huayu capsule on limb-catching capability of rat models of open TBI,and investigate its possible mechanism.DESIGN: Randomized and controlled study.SETTING: Grade 3 Pharmacological Laboratory of TCM, State Administration of TCM, Chengdu University of TCM.MATERIALS: This study was performed from October 2005 to January 2006. Fifty Sprague-Dawley rats of either gender, aged 3 months old, weighing from 190 to 220 g, were involved in this study. Huayu capsule was made and supplied by the Department of TCM Processing of Chengdu University of TCM, Lot No.050121; Xuefuzhuyu oral liquid was manufactured by Jilin Aodong Yanbian Pharmaceutical Industry Co.,Ltd., Lot No. 050406.METHODS: Open right parietal lobe TBI rat models were made as described in references. The involved rat models were randomized into 5 groups according to gender and body mass: model group, high-, middle-,low-dose Huayu capsule groups and Xuefuzhuyu oral liquid group, with 10 rats in each. Rats in the model group were administrated with distilled water of 5 mL/kg; Rats in the high-, middle- and low-dose Huayu capsule groups were administrated with 1.030, 0.515, 0.258 g/kg raw herbs; Rats in the Xuefuzhuyu oral liquid group were administrated with Xuefuzhuyu oral liquid of 5 mL/kg, intragastrically once a day for 7 days successively for all after recovering consciousness from anesthetization. ① One hour after administration on the 6th day, rats in each group were placed on a 100 cm fine straight iron wire paralleling to the ground and 20 cm above the operational table. The time of the rats keeping on the wire was counted and it indicated the nerve-muscle catching capability. The longer the remained time, the better the nerve-muscle catching capability.② Twenty

  3. Protective effect of crocin on acrolein-induced tau phosphorylation in the rat brain.

    Science.gov (United States)

    Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

    2015-01-01

    Acrolein, as a by-product of lipid peroxidation, is implicated in brain aging and in the pathogenesis of oxidative stressmediated neurodegenerative disorders such as Alzheimer's disease (AD). Widespread human exposure to the toxic environmental pollutant that is acrolein renders it necessary to evaluate the effects of exogenous acrolein on the brain. This study investigated the toxic effects of oral administration of 3 mg/kg/day acrolein on the rat cerebral cortex. Moreover, the neuroprotective effects of crocin, the main constituent of saffron, against acrolein toxicity were evaluated. We showed that acrolein decreased concentration of glutathione (GSH) and increased levels of malondialdehyde (MDA), Amyloid-beta (Abeta) and phospho-tau in the brain. Simultaneously, acrolein activated Mitogen-Activated Protein Kinases (MAPKs) signalling pathways. Co-administration of crocin significantly attenuated MDA, Abeta and p-tau levels by modulating MAPKs signalling pathways. Our data demonstrated that environmental exposure to acrolein triggers some molecular events which contribute to brain aging and neurodisorders. Additionally, crocin as an antioxidant is a promising candidate for treatment of neurodegenerative disorders, such as brain aging and AD.

  4. Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+/nestin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+/nestin+ cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was es...

  5. The Function of the Glutamate-Nitric Oxide-cGMP Pathway in Brain in Vivo and Learning Ability Decrease in Parallel in Mature Compared with Young Rats

    Science.gov (United States)

    Piedrafita, Blanca; Cauli, Omar; Montoliu, Carmina; Felipo, Vicente

    2007-01-01

    Aging is associated with cognitive impairment, but the underlying mechanisms remain unclear. We have recently reported that the ability of rats to learn a Y-maze conditional discrimination task depends on the function of the glutamate-nitric oxide-cGMP pathway in brain. The aims of the present work were to assess whether the ability of rats to…

  6. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  7. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

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    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  8. The laboratory rat: Relating its age with human′s

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    Pallav Sengupta

    2013-01-01

    Full Text Available By late 18 th or early 19 th century, albino rats became the most commonly used experimental animals in numerous biomedical researches, as they have been recognized as the preeminent model mammalian system. But, the precise correlation between age of laboratory rats and human is still a subject of debate. A number of studies have tried to detect these correlations in various ways, But, have not successfully provided any proper association. Thus, the current review attempts to compare rat and human age at different phases of their life. The overall findings indicate that rats grow rapidly during their childhood and become sexually mature at about the sixth week, but attain social maturity 5-6 months later. In adulthood, every day of the animal is approximately equivalent to 34.8 human days (i.e., one rat month is comparable to three human years. Numerous researchers performed experimental investigations in albino rats and estimated, in general, while considering their entire life span, that a human month resembles every-day life of a laboratory rat. These differences signify the variations in their anatomy, physiology and developmental processes, which must be taken into consideration while analyzing the results or selecting the dose of any research in rats when age is a crucial factor.

  9. Postnatal development of aminopeptidase (arylamidase) activity in rat brain.

    Science.gov (United States)

    de Gandarias, J M; Ramírez, M; Zulaica, J; Iribar, C; Casis, L

    1989-01-01

    Changes in the activities of Leu- and Arg-arylamidase in rat frontal and parietal cortices and the subcortical area (including thalamus, hypothalamus, and striatum) were examined in the 2nd, 4th, 8th, 12th, and 24th weeks of life. Average levels found in the subcortical region were greater than those in the cortical areas. The most marked changes in enzymatic activity in the course of brain development were found in the subcortical structure. Leu-arylamidase activity increased from the 2nd week up to the 8th week, returning to the 2nd week level at the 12th and 24th weeks. The maximum levels of Arg-arylamidase activity were found at the 4th and 8th weeks. These data suggest that proteolytic activity is involved in the postnatal development of rat brain.

  10. The change in the supply with reduction equivalents in different organs of the rat during aging.

    Science.gov (United States)

    Niedermüller, H; Hofecker, G; Skalicky, M

    1991-01-01

    The rate of metabolic kinetics and the frequency of biological cycles may be correlated with the rate of aging and the maximum life-span potential. Therefore, investigation either into changes with age of such parameters within one species or into differences between species may give some information about the genetic programming of the aging process. Male Sprague-Dawley rats aged 3.5, 7, 12, 17, 23, and 33 months (m) were used to determine the changes with age of those metabolic pathways mentioned in the title, using the liver (LI), kidney (KI), brain (BR), heart (HE) and the skeletal muscle (SM). The maximum percentage of glucose utilization via the pentose pathway, compared to the total glucose utilization, was calculated after intravenous administration of D-[1-14C]- and D-[6-14C]glucose by the determination of the trioses (as lipids) 3 hours after the application. Furthermore, in rats aged 13 and 25 m the kinetics of both glucoses was measured in liver, kidney, heart, brain, skeletal muscle, spleen (SP), and testes (TE) during the first 3 hours after application. Pentose pathway values were calculated. The results indicate a decrease in the glucose utilization via the pentose pathway in the course of aging in liver, kidney, heart and skeletal muscle and a decrease from 3.5 months on in brain, younger rats exhibit a higher rate of glucose utilization via the pentose pathway as do old ones, the reduction of the pentose pathway may possibly be the cause of higher lipofuscin accumulation in the cells of some organs, lacking sufficient reduction equivalents for lipid metabolism.

  11. Greater glucocorticoid receptor activation in hippocampus of aged rats sensitizes microglia.

    Science.gov (United States)

    Barrientos, Ruth M; Thompson, Vanessa M; Kitt, Meagan M; Amat, Jose; Hale, Matthew W; Frank, Matthew G; Crysdale, Nicole Y; Stamper, Christopher E; Hennessey, Patrick A; Watkins, Linda R; Spencer, Robert L; Lowry, Christopher A; Maier, Steven F

    2015-03-01

    Healthy aging individuals are more likely to suffer profound memory impairments following an immune challenge than are younger adults. These challenges produce a brain inflammatory response that is exaggerated with age. Sensitized microglia found in the normal aging brain are responsible for this amplified response, which in turn interferes with processes involved in memory formation. Here, we examine factors that may lead aging to sensitize microglia. Aged rats exhibited higher corticosterone levels in the hippocampus, but not in plasma, throughout the daytime (diurnal inactive phase). These elevated hippocampal corticosterone levels were associated with increased hippocampal 11β-hydroxysteroid dehydrogenase type 1 protein expression, the enzyme that catalyzes glucocorticoid formation and greater hippocampal glucocorticoid receptor (GR) activation. Intracisternal administration of mifepristone, a GR antagonist, effectively reduced immune-activated proinflammatory responses, specifically from hippocampal microglia and prevented Escherichia coli-induced memory impairments in aged rats. Voluntary exercise as a therapeutic intervention significantly reduced total hippocampal GR expression. These data strongly suggest that increased GR activation in the aged hippocampus plays a critical role in sensitizing microglia.

  12. Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats.

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    Pietrelli, A; Lopez-Costa, J; Goñi, R; Brusco, A; Basso, N

    2012-01-27

    Recent research involving human and animals has shown that aerobic exercise of moderate intensity produces the greatest benefit on brain health and behavior. In this study we investigated the effects on cognitive function and anxiety-related behavior in rats at different ages of aerobic exercise, performed regularly throughout life. We designed an aerobic training program with the treadmill running following the basic principles of human training, and assuming that rats have the same physiological adaptations. The intensity was gradually adjusted to the fitness level and age, and maintained at 60-70% of maximum oxygen consumption (max.VO(2)). In middle age (8 months) and old age (18 months), we studied the cognitive response with the radial maze (RM), and anxiety-related behaviors with the open field (OF) and the elevated plus maze (EPM). Aerobically trained (AT) rats had a higher cognitive performance measured in the RM, showing that exercise had a cumulative and amplifier effect on memory and learning. The analysis of age and exercise revealed that the effects of aerobic exercise were modulated by age. Middle-aged AT rats were the most successful animals; however, the old AT rats met the criteria more often than the middle-aged sedentary controls (SC), indicating that exercise could reverse the negative effects of sedentary life, partially restore the cognitive function, and protect against the deleterious effects of aging. The results in the OF and EPM showed a significant decrease in key indicators of anxiety, revealing that age affected most of the analyzed variables, and that exercise had a prominent anxiolytic effect, particularly strong in old age. In conclusion, our results indicated that regular and chronic aerobic exercise has time and dose-dependent, neuroprotective and restorative effects on physiological brain aging, and reduces anxiety-related behaviors.

  13. Effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    许民辉; 代文光; 邓洵鼎

    2002-01-01

    Objective: To study the effects of magnesium sulfate on brain mitochondrial respiratory function in rats after experimental traumatic brain injury and the possible mechanism.Methods: The middle degree brain injury in rats was made by BIM-III multi-function impacting machine. The brain mitochondrial respiratory function was measured with oxygen electrode and the ultra-structural changes were observed with transmission electron microscope (TEM).Results: 1. The brain mitochondrial respiratory stage III and respiration control rate reduced significantly in the untreated groups within 24 and 72 hours. But treated Group A showed certain degree of recovery of respiratory function; treated Group B showed further improvement. 2. Untreated Group, treated Groups A and B had different degrees of mitochondrial ultra-structural damage respectively, which could be attenuated after the treatment with magnesium sulfate.Conclusions: The mitochondrial respiratory function decreases significantly after traumatic brain injury. But it can be apparently improved after magnesium sulfate management along with the attenuated damage of mitochondria discovered by TEM. The longer course of treatment can obtain a better improvement of mitochondrial respiratory function.

  14. Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP.

    Science.gov (United States)

    Rajagopal, Sathyanarayanan; Deb, Ishani; Poddar, Ranjana; Paul, Surojit

    2016-05-01

    The STriatal-Enriched tyrosine Phosphatase (STEP) is involved in the etiology of several age-associated neurologic disorders linked to oxidative stress and is also known to play a role in neuroprotection by modulating glutamatergic transmission. However, the possible effect of aging on STEP level and activity in the brain is still unclear. In this study, using young (1 month), adult (4 months), and aged (18 months) rats, we show that aging is associated with increase in dimerization and loss of activity of STEP. Increased dimerization of STEP is primarily observed in the cortex and hippocampus and is associated with depletion of both reduced and total glutathione levels, suggesting an increase in oxidative stress. Consistent with this interpretation, studies in cell culture models of glutathione depletion and oxidative stress also demonstrate formation of dimers and higher order oligomers of STEP that involve intermolecular disulfide bond formation between multiple cysteine residues. Conversely, administration of N-acetyl cysteine, a major antioxidant that enhances glutathione biosynthesis, attenuates STEP dimerization both in the cortex and hippocampus. The findings indicate that loss of this intrinsic protective response pathway with age-dependent increase in oxidative stress may be a contributing factor for the susceptibility of the brain to age-associated neurologic disorders.

  15. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

    Science.gov (United States)

    Jeong, Sae Im; Shin, Jin A; Cho, Sunghee; Kim, Hye Won; Lee, Ji Yoon; Kang, Jihee Lee; Park, Eun-Mi

    2016-08-01

    Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women.

  16. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

    Institute of Scientific and Technical Information of China (English)

    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

  17. Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function

    Institute of Scientific and Technical Information of China (English)

    胡德志; 周良辅; 朱剑虹

    2004-01-01

    @@ Marrow stromal cells(MSCs) have been reported to transplant into injured brain via intravenous or intraarterial or direct intracerebral administration.1-3 In the present study, we observed that MSCs migrated into the brain, survived and diffeneriated into neural cells after they were injected into the cisterna magna of rats, and that the behavior of the rats after traumatic brain injury (TBI) was improved.

  18. Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

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    Barhoum Rima

    2011-07-01

    Full Text Available Abstract Background GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats. Methods Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old; untreated old rats (O, 103 weeks old; and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1 for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland. Serum levels of hormones (testosterone, IGF-I and insulin were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states. ATP synthesis in isolated mitochondria was determined by an enzymatic method. Results Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS. IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations. Conclusions We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and

  19. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  20. Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging.

    Science.gov (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique

    2009-04-02

    Mitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the E(1alpha) subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling.

  1. Gelation and fodrin purification from rat brain extracts.

    Science.gov (United States)

    Levilliers, N; Péron-Renner, M; Coffe, G; Pudles, J

    1986-06-03

    Extracts from rat brain tissue have been shown to give rise to a gel which exhibits the following features. It is mainly enriched in actin and in a high-molecular-weight protein with polypeptide chains of 235 and 240 kDa, which we identified as fodrin. Tubulin is also a major component of the gel but it appears to be trapped non-specifically during the gelation process. Gelation is pH-, ionic strength- and Ca2+-concentration-dependent, and is optimal under the conditions which promote the interaction between polymerized actin and fodrin. In a similar way to that described for the purification of rat brain actin (Levilliers, N., Péron-Renner, M., Coffe, G. and Pudles, J. (1984) Biochimie 66, 531-537), we used the gelation system as a selective means of recovering fodrin from the mixture of a low-ionic-strength extract from whole rat brain and a high-ionic-strength extract of the particulate fraction. From this gel, fodrin was purified with a good yield by a simple procedure involving gel dissociation in 0.5 M KCl and depolymerization in 0.7 M KI, Bio-Gel A-15m chromatography, followed by ammonium sulfate precipitation.

  2. Brain oxidative stress induced by obstructive jaundice in rats.

    Science.gov (United States)

    Chroni, Elisabeth; Patsoukis, Nikolaos; Karageorgos, Nikolaos; Konstantinou, Dimitris; Georgiou, Christos

    2006-02-01

    The effect of experimental obstructive jaundice on the oxidative status of brain tissues in rats was examined. Twenty-four male Wistar rats were divided into 4 groups: Group I was the control, group II was the sham operated, and groups III and IV were bile duct ligated and killed on the 5th and the 10th day, respectively. Oxidative stress was assessed by measuring the thiol redox state (protein and nonprotein components) and lipid peroxidation level variations in samples from the cerebral cortex, midbrain, and cerebellar tissue in all animals. Results indicated the presence of oxidative stress in the jaundiced animals that was more pronounced on the 10th day as indicated by a decrease in reduced glutathione and protein thiol and an increase in protein disulphide and lipid peroxidation. A dramatic elevation of the level of total nonprotein mixed disulphide level was found specifically in the midbrain in the 10th day group. This suggests an accumulation of nonprotein disulfides other than oxidized glutathione, which remained unchanged, in this particular brain area. This study showed a correlation between experimental obstructive jaundice and the oxidative stress in the rats' brain, implying that a similar pathogenetic mechanism may play a key role in cholestatic liver disease, resulting in hepatic encephalopathy in humans.

  3. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    Science.gov (United States)

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.

  4. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  5. Carbofuran Modulating Functions of Acetylcholinesterase from Rat Brain In Vitro

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    Vivek Kumar Gupta

    2016-01-01

    Full Text Available Carbofuran, a potential environmental xenobiotic, has the ability to cross blood brain barrier and to adversely influence brain functions. In the present study, the impact of carbofuran on the biophysical and biochemical properties of rat brain AChE has been evaluated in vitro. This enzyme was membrane-bound which could be solubilised using Triton-X100 (0.2%, v/v, a nonionic detergent, in the extraction buffer (50 mM phosphate, pH 7.4. The enzyme was highly stable up to one month when stored at -20°C and exhibited optimum activity at pH 7.4 and 37°C. AChE displayed a direct relationship between activity and varying substrate concentrations (acetylthiocholine iodide (ATI by following Michaelis-Menten curve. The Km and Vmax values as computed from the Lineweaver-Burk double reciprocal plot of the data were found to be 0.07 mM and 0.066 µmole/mL/min, respectively. The enzyme exhibited IC50 value for carbofuran equal to 6.0 nM. The steady-state kinetic studies to determine mode of action of carbofuran on rat brain AChE displayed it to be noncompetitive in nature with Ki value equal to 5 nm. These experiments suggested that rat brain AChE was very sensitive to carbofuran and this enzyme might serve as a significant biomarker of carbofuran induced neurotoxicity.

  6. Oxymatrine reduces neuroinflammation in rat brain A signaling pathway

    Institute of Scientific and Technical Information of China (English)

    Jiahui Mao; Yae Hu; Ailing Zhou; Bing Zheng; Yi Liu; Yueming Du; Jia Li; Jinyang Lu; Pengcheng Zhou

    2012-01-01

    Cerebral neuroinflammation models were established by injecting 10 μg lipopolysaccharide into the hippocampus of male Sprague-Dawley rats.The rats were treated with an intraperitoneal injection of 120,90,or 60 mg/kg oxymatrine daily for three days prior to the lipopolysaccharide injection.Twenty-four hours after model induction,the hippocampus was analyzed by real-time quantitative PCR,and the cerebral cortex was analyzed by enzyme-linked immunosorbent assay and western blot assay.The results of the enzyme-linked immunosorbent assay and the real-time quantitative PCR showed that the secretion and mRNA expression of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α were significantly decreased in the hippocampus and cerebral cortex of model rats treated with oxymatrine.Western blot assay and real-time quantitative PCR analysis indicated that toll-like receptor 4 mRNA and protein expression were significantly decreased in the groups receiving different doses of oxymatrine.Additionally,120 and 90 mg/kg oxymatrine were shown to reduce protein levels of nuclear factor-kB p65 in the nucleus and of phosphorylated IkBα in the cytoplasm of brain cells,as detected by western blot assay.Experimental findings indicate that oxymatrine may inhibit neuroinflammation in rat brain via downregulating the expression of molecules in the toll-like receptor 4/nuclear factor-kB signaling pathway.

  7. Cerebrolysin improves memory and ameliorates neuronal atrophy in spontaneously hypertensive, aged rats.

    Science.gov (United States)

    Solis-Gaspar, Carlos; Vazquez-Roque, Ruben A; De Jesús Gómez-Villalobos, Ma; Flores, Gonzalo

    2016-09-01

    The spontaneously hypertensive (SH) rat has been used as an animal model of vascular dementia (VD). Our previous report showed that, SH rats exhibited dendritic atrophy of pyramidal neurons of the CA1 dorsal hippocampus and layers 3 and 5 of the prefrontal cortex (PFC) at 8 months of age. In addition, we showed that cerebrolysin (Cbl), a neurotrophic peptide mixture, reduces the dendritic atrophy in aged animal models. This study aimed to determine whether Cbl was capable of reducing behavioral and neuronal alterations, in old female SH rats. The level of diastolic and systolic pressure was measured every month for the 6 first months and only animals with more than 160 mm Hg of systolic pressure were used. Female SH rats (6 months old) received 6 months of Cbl treatment. Immediately after the Cbl treatment, two behavioral tests were applied, the Morris water maze test for memory and learning and locomotor activity in novel environments. Immediately after the last behavioral test, dendritic morphology was studied with the Golgi-Cox stain procedure followed by a Sholl analysis. Clearly, SH rats with Cbl showed an increase in the dendritic length and dendritic spine density of pyramidal neurons in the CA1 in the dorsal hippocampus and layers 3 and 5 of the PFC. Interestingly, Cbl improved memory of the old SH rats. Our results support the possibility that Cbl may have beneficial effects on the management of brain alterations in an animal model with VD. Synapse 70:378-389, 2016. © 2016 Wiley Periodicals, Inc.

  8. Distinct transcriptional changes in donor kidneys upon brain death induction in rats : Insights in the processes of brain death

    NARCIS (Netherlands)

    Schuurs, TA; Gerbens, F; van der Hoeven, JAB; Ottens, PJ; Kooi, KA; Leuvenink, HGD; Hofstra, RMW; Ploeg, RJ

    2004-01-01

    Brain death affects hormone regulation, inflammatory reactivity and hemodynamic stability. In transplant models, donor organs retrieved from brain dead (BD) rats suffer from increased rates of primary nonfunction and lower graft survival. To unravel the mechanisms behind brain death we have performe

  9. Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and the Severity of Brain Damage in Rats.

    Science.gov (United States)

    Shakova, F M; Barskov, I V; Gulyaev, M V; Prokhorenko, S V; Romanova, G A; Grechko, A V

    2016-07-01

    A correlation between the severity of morphofunctional disturbances and the volume of brain tissue injury determined by MRT was demonstrated on the model of open traumatic brain injury in rats. A relationship between the studied parameters (limb placing and beam walking tests and histological changes) and impact force (the height of load fell onto exposed brain surface) was revealed.

  10. Vitamin E supplementation modulates the biological effects of omega-3 fatty acids in naturally aged rats.

    Science.gov (United States)

    Narayanankutty, Arunaksharan; Kottekkat, Anagha; Mathew, Shaji E; Illam, Soorya P; Suseela, Indu M; Raghavamenon, Achuthan C

    2017-03-01

    Omega-3 fatty acids are well-known class of nutraceuticals with established health benefits. Recently, the oxidation products of these fatty acids are gaining attention, as they are likely to disturb body redox balance. Therefore, the efficacy of omega-3 fats under conditions of diminished antioxidant status, such as aging, is always a concern. Present study assessed the effects of omega-3 fats (DHA and EPA) together with or without vitamin-E in naturally aged rats. It was found that in omega-3 fats alone consumed rats the lipid profile was improved, while in omega-3 fat with vitamin-E-consumed group (OMVE), the hepato protective and antioxidant properties were pronounced, especially the redox status of brain tissue. It is possible that vitamin-E might have reduced the peroxidation of omega-3 fats, thereby allowing their synergistic effects. Hence, the use of vitamin-E along with omega-3 fat may be beneficial under aged conditions.

  11. Photoacoustic imaging for transvascular drug delivery to the rat brain

    Science.gov (United States)

    Watanabe, Ryota; Sato, Shunichi; Tsunoi, Yasuyuki; Kawauchi, Satoko; Takemura, Toshiya; Terakawa, Mitsuhiro

    2015-03-01

    Transvascular drug delivery to the brain is difficult due to the blood-brain barrier (BBB). Thus, various methods for safely opening the BBB have been investigated, for which real-time imaging methods are desired both for the blood vessels and distribution of a drug. Photoacoustic (PA) imaging, which enables depth-resolved visualization of chromophores in tissue, would be useful for this purpose. In this study, we performed in vivo PA imaging of the blood vessels and distribution of a drug in the rat brain by using an originally developed compact PA imaging system with fiber-based illumination. As a test drug, Evans blue (EB) was injected to the tail vein, and a photomechanical wave was applied to the targeted brain tissue to increase the permeability of the blood vessel walls. For PA imaging of blood vessels and EB distribution, nanosecond pulses at 532 nm and 670 nm were used, respectively. We clearly visualized blood vessels with diameters larger than 50 μm and the distribution of EB in the brain, showing spatiotemporal characteristics of EB that was transvascularly delivered to the target tissue in the brain.

  12. Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats.

    Science.gov (United States)

    Du, Fang; Qian, Zhong-Ming; Luo, Qianqian; Yung, Wing-Ho; Ke, Ya

    2015-08-01

    Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor-1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad-hepcidin emerges as a new pharmacological treatment and prevention for iron-associated neurodegenerative disorders.

  13. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats.

    Science.gov (United States)

    Zhao, Jinbing; Chen, Zhi; Xi, Guohua; Keep, Richard F; Hua, Ya

    2014-10-01

    Acute post-traumatic ventricular dilation and hydrocephalus are relatively frequent consequences of traumatic brain injury (TBI). Several recent studies have indicated that high iron levels in brain may relate to hydrocephalus development after intracranial hemorrhage. However, the role of iron in the development of post-traumatic hydrocephalus is still unclear. This study was to determine whether or not iron has a role in hydrocephalus development after TBI. TBI was induced by lateral fluid-percussion in male Sprague-Dawley rats. Some rats had intraventricular injection of iron. Acute hydrocephalus was measured by magnetic resonance T2-weighted imaging and brain hemorrhage was determined by T2* gradient-echo sequence imaging and brain hemoglobin levels. The effect of deferoxamine on TBI-induced hydrocephalus was examined. TBI resulted in acute hydrocephalus at 24 h (lateral ventricle volume: 24.1 ± 3.0 vs. 9.9 ± 0.2 mm(3) in sham group). Intraventricular injection of iron also caused hydrocephalus (25.7 ± 3.4 vs. 9.0 ± 0.6 mm(3) in saline group). Deferoxamine treatment attenuated TBI-induced hydrocephalus and heme oxygenase-1 upregulation. In conclusion, iron may contribute to acute hydrocephalus after TBI.

  14. Blood-Brain Barrier Breakdown in the Aging Human Hippocampus

    Science.gov (United States)

    Montagne, Axel; Barnes, Samuel R.; Sweeney, Melanie D.; Halliday, Matthew R.; Sagare, Abhay P.; Zhao, Zhen; Toga, Arthur W.; Jacobs, Russell E.; Liu, Collin Y.; Amezcua, Lilyana; Harrington, Michael G.; Chui, Helena C.; Law, Meng; Zlokovic, Berislav V.

    2014-01-01

    Summary The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer’s disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic contrast-enhanced magnetic resonance imaging protocol with high spatial and temporal resolutions to quantify regional BBB permeability in the living human brain, we show an age-dependent BBB breakdown in the hippocampus, a region critical for learning and memory that is affected early in AD. The BBB breakdown in the hippocampus and its CA1 and dentate gyrus subdivisions worsened with mild cognitive impairment that correlated with injury to BBB-associated pericytes, as shown by the cerebrospinal fluid analysis. Our data suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to cognitive impairment. PMID:25611508

  15. Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats.

    Science.gov (United States)

    Meng, Qingying; Wong, Yee Ting; Chen, Jie; Ruan, Runsheng

    2007-03-01

    We have previously reported the changes of mitochondrial function and/or antioxidative enzyme efficiency in a few organs of rats as a result of aging. However, there is a further need to reach a conclusion about their interactions in biological functions based on other evaluation tips like the usage of advanced methods and the exploring of crucial biochemical parameters. Therefore, we investigated the mitochondrial inner membrane functional integrity by the analysis of respiration control ratio and membrane potential in the liver and brain of young (8 months) and old (26 months) Fischer 344 rats. The disintegration of mitochondrial membrane integrity was determined higher in the liver of old rats than that of young rats. This was well correlated with the decrease of total superoxide dismutase (SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase activities in most of the organs, except for the increase of catalase activity in heart of old rats. Similarly, the protein expressions of these enzymes were down regulated in the liver and kidney of old rats. Taken together, we suggest that the mitochondrial malfunction in old rats is associated with the decrease of antioxidative enzyme efficiency. And the data are also discussed with changes in the results from inter-laboratories.

  16. Tart cherry supplementation improves working memory, hippocampal inflammation, and autophagy in aged rats.

    Science.gov (United States)

    Thangthaeng, Nopporn; Poulose, Shibu M; Gomes, Stacey M; Miller, Marshall G; Bielinski, Donna F; Shukitt-Hale, Barbara

    2016-12-01

    High consumption of fruits and vegetables has been associated with reduced risk of debilitating diseases and improved cognition in aged populations. These beneficial effects have been attributed to the phytochemicals found in fruits and vegetables, which have previously been shown to be anti-inflammatory and modulate autophagy. Tart cherries contain a variety of potentially beneficial phytochemicals; however, little research has been done to investigate the effects of tart cherry on the aging brain. Therefore, the purpose of this study was to determine if tart cherry supplementation can improve cognitive and motor function of aged rats via modulation of inflammation and autophagy in the brain. Thirty 19-month-old male Fischer 344 rats were weight-matched and assigned to receive either a control diet or a diet supplemented with 2 % Montmorency tart cherry. After 6 weeks on the diet, rats were given a battery of behavioral tests to assess for strength, stamina, balance, and coordination, as well as learning and working memory. Although no significant effects were observed on tests of motor performance, tart cherry improved working memory of aged rats. Following behavioral testing, the hippocampus was collected for western/densitometric analysis of inflammatory (GFAP, NOX-2, and COX-2) and autophagy (phosphorylated mTOR, Beclin 1, and p62/SQSTM) markers. Tart cherry supplementation significantly reduced inflammatory markers and improved autophagy function. Daily consumption of tart cherry reduced age-associated inflammation and promoted protein/cellular homeostasis in the hippocampus, along with improvements in working memory. Therefore, addition of tart cherry to the diet may promote healthy aging and/or delay the onset of neurodegenerative diseases.

  17. Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

    Science.gov (United States)

    Niggeschulze, A; Kast, A

    1994-01-01

    The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20 virgin females were inseminated per age group. The copulation rate did not differ between the groups. From the maternal age of 12 months, the pregnancy rate was significantly decreased, from the age of 9 months, the litter values were significantly lowered and the resorption rates were increased. Maternal age did not influence the incidence of fetal variations and malformations. Additionally, the chromosomal aberration rate in the bone marrow was evaluated in male and female rats. Twelve animals of each sex were scheduled per group, and studied at the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate increased continuously from 0.18 through 3%, while in females the increase continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When testing new compounds for embryotoxicity or genotoxicity in female rats, the animals should be of comparable age to man in order to avoid a misinterpretation of spontaneous abnormalities. From these studies, however, it was concluded that the use of higher age groups of female rats in teratogenicity studies would not improve the risk assessment.

  18. Systemic HMGB1 neutralization prevents postoperative neurocognitive dysfunction in aged rats

    Directory of Open Access Journals (Sweden)

    Niccolo Terrando

    2016-10-01

    Full Text Available Postoperative neurocognitive disorders are common complications in elderly patients following surgery or critical illness. High mobility group box 1 protein (HMGB1 is rapidly released after tissue trauma and critically involved in response to sterile injury. Herein we assessed the role of HMGB1 after liver surgery in aged rats and explored the therapeutic potential of a neutralizing anti-HMGB1 monoclonal antibody in a clinically relevant model of postoperative neurocognitive disorders. 19-22 months Sprague Dawley rats were randomly assigned as: (1 control with saline; (2 surgery, a partial hepatolobectomy under sevoflurane anesthesia and analgesia, + immunoglobulin G as control antibody; (3 surgery + anti-HMGB1. A separate cohort of animals was used to detect His-tagged HMGB1 in the brain. Systemic anti-HMGB1 antibody treatment exerted neuroprotective effects preventing postoperative memory deficits and anxiety in aged rats by preventing surgery-induced reduction of phosphorylated cyclic AMP response element-binding protein in the hippocampus. Although no evident changes in the intracellular distribution of HMGB1 in hippocampal cells were noted after surgery, HMGB1 levels were elevated on day 3 in rat plasma samples. Experiments with tagged HMGB1 further revealed a critical role of systemic HMGB1 to enable an access to the brain and causing microglial activation. Overall, these data demonstrate a pivotal role for systemic HMGB1 in mediating postoperative neuroinflammation. This may have direct implications for common postoperative complications like delirium and postoperative cognitive dysfunction.

  19. Lucid dreaming: an age-dependent brain dissociation.

    Science.gov (United States)

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation.

  20. Age-related hearing loss: ear and brain mechanisms.

    Science.gov (United States)

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  1. Brain Plasticity and Motor Practice in Cognitive Aging

    Directory of Open Access Journals (Sweden)

    Liuyang eCai

    2014-03-01

    Full Text Available For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

  2. Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2017-02-01

    Metformin, a biguanide drug commonly used to treat type 2 diabetes, has been noted to function as a caloric restriction mimetic. Its antidiabetic effect notwithstanding, metformin is currently being considered an antiaging drug candidate, although the molecular mechanisms have not yet been unequivocally established. This study aims to examine whether short-term metformin treatment can provide protective effects against oxidative stress in young and old-age rats. Young (age 4 months) and old (age 24 months) male Wistar rats were treated with metformin (300 mg/kg b.w.) for 4 weeks. At the end of the treatment period, an array of biomarkers of oxidative stress were evaluated, including plasma antioxidant capacity measured in terms of ferric reducing ability of plasma (FRAP), reactive oxygen species (ROS), lipid peroxidation (MDA), reduced glutathione (GSH), total plasma thiol (SH), plasma membrane redox system (PMRS), protein carbonyl (PCO), advanced oxidation protein products (AOPPs), and advanced glycation end products (AGEs) in control and experimental groups. Metformin treatment resulted in an increase in FRAP, GSH, SH, and PMRS activities in both age groups compared to respective controls. On the other hand, treated groups exhibited significant reductions in ROS, MDA, PCO, AOPP, and AGE level. Save for FRAP and protein carbonyl, the effect of metformin on all other parameters was more pronounced in old-aged rats. Metformin caused a significant increase in the PMRS activity in young rats, however, the effect was less pronounced in old rats. These findings provide evidence with respect to restoration of antioxidant status in aged rats after short-term metformin treatment. The findings substantiate the putative antiaging role of metformin.

  3. Effect of cardiac arrest on cognitive impairment and hippocampal plasticity in middle-aged rats.

    Directory of Open Access Journals (Sweden)

    Charles H Cohan

    Full Text Available Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1 establishing a model of CA in nine month old middle-aged rats; and 2 to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning and field recordings (long-term potentiation and paired-pulse facilitation were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction.

  4. Elemental distribution in brain of wistar rats by X-ray microfluorescence with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Lab. de Instrumentacao Nuclear]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos; Oliveira, Luis F. de [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria da Graca T. do [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Nutricao]. E-mail: tcarmo@editema.com.br; Rocha, Monica S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Farmacologia]. E-mail: mrocha@farmaco.ufrj.br; Moreira, Silvana [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Civil]. E-mail: silvana@fec.unicamp.br; Correa Junior, Jose D.; Martinez, Ana Maria B. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Histologia]. E-mail: martinez@histo.ufrj.br

    2005-07-01

    The main goal of this research is to study the changes in the elemental distribution in brain rats, due the knowledge of the spatial distribution and the local concentration of trace elements in tissues have great importance since trace elements are involved in many biological functions of living organisms. For perform this research, Wistar rats with different ages (3, 48 and 72 weeks) were used. The microfluorescence measurements were carried out in a standard geometry of 45 deg/45 deg, exciting with a white beam and using a conventional system collimation (orthogonal slits) in the XRF beamline at the Synchrotron Light National Laboratory (Campinas, Brazil). The following elements were studied: P, S, Cl, K, Ca, Fe, and Zn. Among these elements, Fe and Zn are related with Parkinson and Alzheimer diseases, respectively. By the elemental maps, we can observe that the distribution of zinc was more pronounced in the hippocampus area, the distribution of iron was more conspicuous in the cortical region and bellows the thalamus and, moreover potassium and chlorine distributions were more present in the cortical area. Although, the small statistic, we can view that almost all measured elements are present in lower intensity in brains of rats with 3 weeks, and are usually the same for the other ages studied. (author)

  5. Hyperglycemia induces protein nonenzymeatic glycosylation in brain neurons of diabetic rats at early stage

    Institute of Scientific and Technical Information of China (English)

    Jingsheng Hu; Xueyi Ma; Shuli Sheng

    2007-01-01

    BACKGROUND: Protein nonenzymatic glycosylation is supposed to be one of mechanisms for chronic complications development in diabetes mellitus, and therefore, might play an important role in the neuronal degeneration.OBJECTIVE: To study the protein nonenzymatic glycosylation in brain neurons of diabetic rats, and to analyze the pathway of neuronal degeneration at the early stage of hyperglymecia.DESIGN: Randomized controlled animal experiment.SETTING: Department of Endocrinology, First hospital Affiliated to General Hospital of Chinese PLA and Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University.MATERIALS: Thirty-five male Wistar rats (grade Ⅱ), aged 3 months old, and 11 male purebred Kunming mice (grade Ⅲ) without special pathogen, aged 3 months old, were provided by the Animal Room of Capital Medical University.METHODS: This experiment was carried out in the Beijing Laboratory for Brain Aging, Xuanwu Hospital Affiliated to Capital Medical University in 1998. The rats in the diabetic model group were intraperitoneally injected into 10 g/L STZ according to 60 mg/kg to establish rat models of diabetes mellitus. The blood glucose and body mass of rats in each group were determined respectively at 1, 2 and 3 months after modeling. The antibodies of advanced glycosylation end products (AGEs) of bovine serum albumin (anti-BSA) were self-prepared: ①The antigen of AGEs-BSA was prepared.②Eleven male Kuming mice (grade Ⅱ) of 3 months old without special pathogen were selected to inoculate AGEs-BSA. ③ The animals were immunized. ④Primary purification and detection of poly-antibodies of AGEs: the AGEs were performed immunohistochemical examination at 1 month after diabetic modeling by ELISA method.MAIN OUTCOME MEASURES: ① Detection results of blood glucose and body mass of rats in two groups at different time points. ② Determination of polyclonal antibody titer of AGEs-BSA. ③ Changes in immunohistochemical image of

  6. Auditory event-related brain potentials for an early discrimination between normal and pathological brain aging

    Institute of Scientific and Technical Information of China (English)

    Juliana Dushanova; Mario Christov

    2013-01-01

    The brain as a system with gradually decreasing resources maximizes its chances by reorganizing neural networks to ensure efficient performance. Auditory event-related potentials were recorded in 28 healthy volunteers comprising 14 young and 14 elderly subjects in auditory discrimination motor task (low frequency tone – right hand movement and high frequency tone – left hand movement). The amplitudes of the sensory event-related potential components (N1, P2) were more pronounced with increasing age for either tone and this effect for P2 amplitude was more pronounced in the frontal region. The latency relationship of N1 between the groups was tone-dependent, while that of P2 was tone-independent with a prominent delay in the elderly group over all brain regions. The amplitudes of the cognitive components (N2, P3) diminished with increasing age and the hemispheric asymmetry of N2 (but not for P3) reduced with increasing age. Prolonged N2 latency with increasing age was widespread for either tone while between-group difference in P3 latency was tone-dependent. High frequency tone stimulation and movement requirements lead to P3 delay in the elderly group. The amplitude difference of the sensory components between the age groups could be due to a general greater alertness, less expressed habituation, or decline in the ability to retreat attentional resources from the stimuli in the elderly group. With aging, a neural circuit reorganization of the brain activity affects the cognitive processes. The approach used in this study is useful for an early discrimination between normal and pathological brain aging for early treatment of cognitive alterations and dementia.

  7. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    Science.gov (United States)

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction.

  8. The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability.

    Science.gov (United States)

    Blau, Christoph W; Cowley, Thelma R; O'Sullivan, Joan; Grehan, Belinda; Browne, Tara C; Kelly, Laura; Birch, Amy; Murphy, Niamh; Kelly, Aine M; Kerskens, Christian M; Lynch, Marina A

    2012-05-01

    In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

  9. Astrogliosis in the brain of obese Zucker rat: a model of metabolic syndrome.

    Science.gov (United States)

    Tomassoni, Daniele; Nwankwo, Innocent Ejike; Gabrielli, Maria Gabriella; Bhatt, Siddhartha; Muhammad, Abdul Bari; Lokhandwala, Mustafa F; Tayebati, Seyed Khosrow; Amenta, Francesco

    2013-05-24

    Metabolic syndrome (MetS) is a disorder characterized primarily by the development of insulin resistance. Insulin resistance and subsequent hyperinsulinemia, originating from abdominal obesity, increases the risk of cerebrovascular and cardiovascular disease and all-cause mortality. Obesity is probably a risk factor for Alzheimer's disease and vascular dementia and is associated with impaired cognitive function. The obese Zucker rat (OZR) represents a model of type 2 diabetes exhibiting a moderate degree of arterial hypertension and of increased oxidative stress. To clarify the possible relationships between MetS and brain damage, the present study has investigated brain microanatomy in OZRs compared with their littermate controls lean Zucker rats (LZRs). Male OZRs and LZRs of 12 weeks of age were used. Their brain was processed for immunochemical and immunohistochemical analysis of glial fibrillary acidic protein (GFAP). In frontal and parietal cortex of OZRs a significant increase in the number of GFAP immunoreactive astrocytes was observed. Similar findings were found in the hippocampus, where an increased number of GFAP immunoreactive astrocytes were detected in the CA1 and CA3 subfields and dentate gyrus of OZRs compared to the LZRs. These findings indicating the occurrence of brain injury accompanied by astrogliosis in OZRs suggest that these rats, developed as an animal model of type 2 diabetes, may also represent a model for assessing the influence of MetS on brain. The identification of neurodegenerative changes in OZRs may represent the first step for better characterizing neuronal involvement in this model of MetS and possible treatment for countering it.

  10. Gastrodin protects neonatal rat brain against hypoxic-ischemic encephalopathy Acute therapeutic drug effects

    Institute of Scientific and Technical Information of China (English)

    Yanjun Niu; Zhengyong Jin

    2008-01-01

    BACKGROUND:Pharmacological experiments have demonstrated that gastrodin has a protective effect on neonatal rat brain subjected to hypoxia-ischemia; however,the underlying mechanism has not been fully elucidated. OBJECTIVE:The aim of this study was to investigate the acute therapeutic effects of gastrodin by observing prostaglandin B2 and 6-keto-prostaglandin F 1 a in brain issue of neonatal rats that received gastrodin injections immediately after hypoxia-ischemia.DESIGN:Single-factor design.SETTING:Department of Pediatrics,Affiliated Hospital of Yanbian University. MATERIALS:This study was performed in the Laboratory of the Department of Pediatrics,Affiliated Hospital of Yanbian University(key laboratory of provincial Health Department)from April to December 2003.Fifty-five Wistar rats of either gender,aged 7 days,were provided by the Laboratory Animal Center of Affiliated Hospital of Yanbian University.The rats were randomly divided into normal control(n=10), model(n=15),gastrodin-treated(n=15),and Danshen-treated(n=15)groups.The protocol was performed in accordance with guidelines from the Institute of Health Sciences for the use and care of animals.The following reagents were.used:Gastrodin(Sancai Medicine Group Co.,Ltd.,Zhongshan,Guangdong Province,China;component:gastrodin),Danshen(Conba Stock Company,Jinhua,Zhengjiang Province,China; component:salvia miltiorrhiza),and reagent kits for 125I-prostaglandin B2 and 125I-6-prostaglandin F 1 a (Research and Development Center for Science and Technology,General Hospital of Chinese PLA). METHODS:Rats in the normal control group received no treatment.Rats in the remaining 3 groups were anesthetized,followed by ligation of the left common carotid artery.One hour later,the rats were placed in a closed hypoxic box and allowed to inhale 8% oxygen-air(2.0-3.0 L/min)for 2 hours to develop hypoxic-ischemic encephalopathy.Immediately after lesion,rats in the gastrodin and Danshen-treated groups were intraperitoneally

  11. In utero exposure to microwave radiation and rat brain development.

    Science.gov (United States)

    Merritt, J H; Hardy, K A; Chamness, A F

    1984-01-01

    Timed-pregnancy rats were exposed in a circular waveguide system starting on day 2 of gestation. The system operated at 2,450 MHz (pulsed waves; 8 microseconds PW; 830 pps). Specific absorption rate (SAR) was maintained at 0.4 W/kg by increasing the input power as the animals grew in size. On day 18 of gestation the dams were removed from the waveguide cages and euthanized; the fetuses were removed and weighed. Fetal brains were excised and weighed, and brain RNA, DNA and protein were determined. Values for measured parameters of the radiated fetuses did not differ significantly from those of sham-exposed fetuses. A regression of brain weight on body weight showed no micrencephalous fetuses in the radiation group when using as a criterion a regression line based on two standard errors of the estimate of the sham-exposed group. In addition, metrics derived from brain DNA (ie, cell number and cell size) showed no significant differences when radiation was compared to sham exposure. We conclude that 2,450-MHz microwave radiation, at an SAR of 0.4 W/kg, did not produce significant alterations in brain organogenesis.

  12. Structure of cristae in cardiac mitochondria of aged rat

    OpenAIRE

    Riva, Alessandro; Tandler, Bernard; Lesnefsky, Edward J.; Conti, Gabriele; Loffredo, Felice; Vazquez, Edwin; Charles L Hoppel

    2006-01-01

    Interfibrillar mitochondria (IFM) of the heart in aged Fischer 344 rats show a biochemical defect which might be reflected in their morphology. We examined by high resolution scanning electron microscopy over 5,500 mitochondria to determine if a concomitant structural alteration existed. This methodology provides a means of examining mitochondrial cristae in three dimensions. Cristae of in situ subsarcolemmal mitochondria (SSM) and of IFM in both 6 and 24 month old Fischer rats are predominan...

  13. Gene Expression Profiling during Pregnancy in Rat Brain Tissue.

    Science.gov (United States)

    Mann, Phyllis E

    2014-03-04

    The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases "expectant brain" and "maternal brain". Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  14. Measurement of tritiated norepinephrine metabolism in intact rat brain

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    Levitt, M.; Kowalik, S.; Barkai, A.I. (New York State Psychiatric Inst., New York (USA))

    1983-06-01

    A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing (/sup 3/H)NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in the rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism.

  15. Characteristics of muscarinic acetylcholine receptors in rat brain.

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    Nukina,Itaru

    1983-06-01

    Full Text Available Characteristics of muscarinic acetylcholine (ACh receptors were studied in the rat central nervous system (CNS using 3H-quinuclidinyl benzilate (QNB, an antagonist of muscarinic ACh receptors. Scatchard analysis indicated that the rat CNS had a single 3H-QNB binding site with an apparent dissociation constant (Kd of 5.0 X 10(-10 M. Li+, Zn++ and Cu++ had strong effects on 3H-QNB binding which indicates that these metal ions might play important roles at muscarinic ACh receptor sites in the brain. Since antidepressants and antischizophrenic drugs displaced the binding of 3H-QNB, the anticholinergic effects of these drugs need to be taken into account when they are applied clinically. The muscarinic ACh receptor was successfully solubilized with lysophosphatidylcholine. By gel chromatography, with a Sepharose 6B column, the solubilized muscarinic ACh receptor molecule eluted at the fraction corresponding to a Stokes' radius of 6.1 nm. With the use of sucrose-density-gradient centrifugation, the molecular weight of the solubilized muscarinic ACh receptor was determined to be about 90,000 daltons. The regional distribution of 3H-QNB binding in rat brain was examined, and the highest level of 3H-QNB binding was found to be in the striatum followed by cerebral cortex and hippocampus, indicating that muscarinic ACh mechanisms affect CNS function mainly through these areas.

  16. 敦煌大宝胶囊对衰老大鼠脑组织NO/NOS表达水平及钙平衡的影响%Effect of DHDB on NO and NOS Expression Levels and Calcium Homeostasis in Brain Tissue of Aging Rats

    Institute of Scientific and Technical Information of China (English)

    程容; 成映霞; 段永强; 梁玉杰; 王道坤; 朱立鸣

    2011-01-01

    Objective: To explore the effect of DHDB on NO/NOS expression levels and calcium homeostasis in brain tissue of aging model rats. Methods: The subacutely aging model rats were made by injecting D-gal into abdominal cavity continually, and NO、NOS、Ca2+ -ATPase and Ca2+ levels in brain tissue were evaluated. Results: The NO, NOS and Ca2+levels in model group were downregulated ( P < 0.05 ), Ca2 + -ATPase levels in that was increased significantly ( P <0.05). After treated with DHDB, NO, NOS and Ca2 + levels were upregulated ( P < 0.05 ) , Ca2 + levels was reduced significantly (P < 0.05 ). Conclusions: The results demonstrated that DHDB can regulate metabolism of NO, NOS and Calcium Homeostasis in brain tissue.%目的:探讨郭煌大宝胶囊对衰老模型大鼠脑组织NO/NOS表达水平及钙平衡的影响.方法:采用D-半乳糖建立大鼠衰老模型,测定各组大鼠脑组织内NO/NOS表达水平、Ca~2-ATPas.活性以及Ca~2含量.结果:模型组大鼠脑组织内NO/NOS水平、Ca~2+含量显著升高(P <0.05),Ca~2+-ATPase活性显著降低(P<0.05);经郭煌大宝胶囊治疗后,大鼠脑组织内NO/NOS水平、Ca~2+含量显著降低(P < 0.05),Ca~2+-ATPase活性显著升高(P<0.05).结论:郭煌大宝胶囊具有调节衰老大鼠脑组织NO/NOS表达水平以及钙平衡的作用.

  17. Indestructible plastic: The neuroscience of the new aging brain

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    Constance eHolman

    2014-04-01

    Full Text Available In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: the cognitive neuroscience of the normal aging. This complex process, once dubbed as inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

  18. Age at developmental cortical injury differentially Alters corpus callosum volume in the rat

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    Rosen Glenn D

    2007-11-01

    Full Text Available Abstract Background Freezing lesions to developing rat cortex induced between postnatal day (P one and three (P1 – 3 lead to malformations similar to human microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case 1. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity 1234, we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments 567. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90, were further analyzed for changes in corpus callosum volume. Results Results showed a significant main effect of Treatment on corpus callosum volume [F (1,57 = 10.2, P Conclusion Decrements in corpus callosum volume in the P1 and 3 lesion groups are consistent with the reductions in brain weight and cortical volume previously reported for microgyric rats 18. Current results suggest that disruption to the cortical plate during early postnatal development may lead to more widely dispersed neurovolumetric anomalies and subsequent behavioral impairments 1, compared with injury that occurs later in development. Further, these results suggest that in a human clinical setting decreased

  19. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats.

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    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping

    2015-05-01

    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  20. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

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    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  1. Brain computed tomography findings of aged schizophrenics; Comparison with healthy aged controls and aged schizophrenics with a history of psychosurgery

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    Oomori, Masao; Koshino, Yoshifumi; Murata, Tetsuhito; Murata, Ichirou; Tani, Kazuhiko; Horie, Tan; Isaki, Kiminori (Fukui Medical School, Matsuoka (Japan))

    1992-05-01

    Brain CT was performed in a total of 30 aged schizophrenic patients, consisting of 20 with no history of psychosurgery (lobotomy) and the other 10 lobotomized patients. The CT findings were compared with those from healthy aged persons. The group of schizophrenic patients had marked atrophy of the frontal lobe and dilatated Sylvian fissure as compared with the control group. There was no significant difference in ventricular factors between the two groups. These findings may have implications for the different mechanisms of the occurrence of atrophied brain surface and enlarged ventricle. The cerebral cortex involved in the occurrence of schizophrenia may be affected by aging-related cerebral atrophy, in addition to the morphological changes due to schizophrenia. Thus, schizophrenic cerebral atrophy was more noticeable than physiological aging-related atrophy. However, enlargement of the ventricle in the schizophrenic group progressed with aging in the same manner as that in the normal group. In comparing schizophrenic patients with or without a history of lobotomy, atrophy of the brain surface and enlargement of the ventricle were more marked in the lobotomized patients than the non-lobotomized patients. This confirmed that lobotomy, as well as surgical scar, is involved in the morphology of schizophrenic brain. (N.K.).

  2. Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

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    R.L. Figueira

    2016-01-01

    Full Text Available Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC. This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group: 1 preterm control (PTC, 2 preterm ventilated (PTV, 3 preterm asphyxiated (PTA, 4 preterm asphyxiated and ventilated (PTAV, 5 term control (TC, 6 term ventilated (TV, 7 term asphyxiated (TA, and 8 term asphyxiated and ventilated (TAV. We measured body, brain, and intestine weights and respective ratios [(BW, (BrW, (IW, (BrW/BW and (IW/BW]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus and intestine (jejunum/ileum tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP. IW was lower in the TA than in the other terms (P<0.05, and the IW/BW ratio was lower in the TA than in the TAV (P<0.005. PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex and TA (cortex/hippocampus (P<0.005. I-FABP was higher in PTAV (P<0.005 and TA (ileum (P<0.05. I-FABP expression was increased in PTAV subgroup (P<0.0001. Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

  3. Cerebral metabolic responses to meta-chlorophenylpiperazine are reduced during its chronic administration to young and aged rats.

    Science.gov (United States)

    Freo, U; Larson, D M; Soncrant, T T

    1993-01-01

    The effects of the 5-HT agonist meta-chlorophenylpiperazine (MCPP) on regional cerebral metabolic rates for glucose (rCMRglc) were measured in 3- and 24-month-old rats that were not pretreated or were pretreated for 2 weeks with continuous infusion of saline or MCPP. rCMRglc were measured using the quantitative autoradiographic [14C]2-deoxy-D-glucose technique in 71 brain regions at 15 min after acute administration of MCPP 2.5 mg/kg. In the absence of chronic pretreatment, intraperitoneal MCPP 2.5 mg/kg produced widespread rCMRglc reductions (41 brain areas) in 3-month-old rats and more limited rCMRglc decreases (8 brain areas) in 24-month-old rats. After chronic treatment, MCPP failed to reduce rCMRglc in any region of either group of rats. These findings indicate that mechanisms of downregulation of response to MCPP are functional in young and aged rats and suggest that the age-related reduction in rCMRglc responses to acute MCPP in non-pretreated animals may be due to compensation for age-related losses of 5-HT terminals.

  4. Four-month enriched environment prevents myelinated fiber loss in the white matter during normal aging of male rats.

    Science.gov (United States)

    Yang, Shu; Lu, Wei; Zhou, De-shan; Tang, Yong

    2015-01-01

    White matter degenerates with normal aging and accordingly results in declines in multiple brain functions. Previous neuroimaging studies have implied that the white matter is plastic by experiences and contributory to the experience-dependent recovery of brain functions. However, it is not clear how and how far enriched environment (EE) plays a role in the white matter remodeling. Male rats exhibit earlier and severer age-related damages in the white matter and its myelinated fibers than female rats; therefore, in this current study, 24 middle-aged (14-month-old) and 24 old-aged (24-month-old) male SD rats were randomly assigned to an EE or standard environment (SE) for 4 months prior to Morris water maze tests. Five rats from each group were then randomly sampled for stereological assessment of the white matter. Results revealed that EE could somewhat induce improvement of spatial learning and significantly increase the white matter volume, the myelinated fiber volume and the myelinated fiber length during normal aging. The EE-induced improvement of spatial learning ability was significantly correlated with the EE-induced increase of the white matter and its myelinated fibers. We suggested that exposure to an EE could delay the progress of age-related changes in the white matter and the effect could extend to old age.

  5. Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

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    Caitlin S Latimer

    Full Text Available Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

  6. Influence of Patient Age on Angioarchitecture of Brain Arteriovenous Malformations

    Science.gov (United States)

    Hetts, Steven W.; Cooke, Daniel L.; Nelson, Jeffrey; Gupta, Nalin; Fullerton, Heather; Amans, Matthew R.; Narvid, Jared A.; Moftakhar, Parham; McSwain, Hugh; Dowd, Christopher F.; Higashida, Randall T.; Halbach, Van V.; Lawton, Michael T.; Kim, Helen

    2014-01-01

    Background and Purpose To determine if clinical and angioarchitectural features of brain AVMs differ between children and adults. Materials and Methods A prospectively collected institutional database of all patients diagnosed with brain AVMs since 2001 was queried. Demographic, clinical, and angioarchitecture information was summarized and analyzed with univariable and multivariable models. Results Results often differed when age was treated as a continuous variable as opposed to dividing subjects into children (≤18 years; n=203) versus adults (>18 years; n=630). Children were more likely to present with AVM hemorrhage than adults (59% vs. 41%, p6 cm compared to 37.1 years for <3 cm), this was not significantly different between children and adults (p=0.069). Exclusively deep venous drainage was more common in younger subjects both when age was treated continuously (p=0.04), or dichotomized (p<0.001). Venous ectasia was more common with increasing age (mean, 39.4 years with ectasia compared to 31.1 years without ectasia) and when adults were compared to children (52% vs. 35%, p<0.001). Patients with feeding artery aneurysms presented at later average age (44.1 years) than those without such aneurysms (31.6 years); this observation persisted when comparing children to adults (13% vs. 29%, p<0.001). Conclusion Although children with brain AVMs were more likely to come to clinical attention due to hemorrhage than adults, venous ectasia and feeding artery aneurysms were underrepresented in children, suggesting that these particular high risk features take time to develop. PMID:24627452

  7. Type 3 Adenylyl Cyclase and Somatostatin Receptor 3 Expression Persists in Aged Rat Neocortical and Hippocampal Neuronal Cilia

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    Sarah eGuadiana

    2016-05-01

    Full Text Available The primary cilia of forebrain neurons assemble around birth and become enriched with neuromodulatory receptors. Our understanding of the permanence of these structures and their associated signaling pathways in the aging brain is poor, but they are worthy of investigation because disruptions in neuronal cilia signaling have been implicated in changes in learning and memory, depression-like symptoms, and sleep anomalies. Here, we asked whether neurons in aged forebrain retain primary cilia and whether the staining characteristics of aged cilia for type 3 adenylyl cyclase (ACIII, somatostatin receptor 3 (SSTR3, and pericentrin resemble those of cilia in younger forebrain. To test this, we analyzed immunostained sections of forebrain tissues taken from young and aged male Fischer 344 (F344 and Fischer 344 x Brown Norway (F344 x BN rats. Analyses of ACIII and SSTR3 in young and aged cortices of both strains of rats revealed that the staining patterns in the neocortex and hippocampus were comparable. Virtually every NeuN positive cell examined possessed an ACIII positive cilium. The lengths of ACIII positive cilia in neocortex were similar between young and aged for both strains, whereas in F344 x BN hippocampus, the cilia lengths increased with age in CA1 and CA3, but not in DG. Additionally, the percentages of ACIII positive cilia that were also SSTR3 positive did not differ between young and aged tissues in either strain. We also found that pericentrin, a protein that localizes to the basal bodies of neuronal cilia and functions in primary cilia assembly, persisted in aged cortical neurons of both rat strains. Collectively, our data show that neurons in aged rat forebrain possess primary cilia and that these cilia, like those present in younger brain, continue to localize ACIII, SSTR3, and pericentrin. Further studies will be required to determine if the function and signaling pathways regulated by cilia are similar in aged compared to young

  8. Cerebrolysin attenuates blood-brain barrier and brain pathology following whole body hyperthermia in the rat.

    Science.gov (United States)

    Sharma, Hari Shanker; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Johanson, Conrad E

    2010-01-01

    The possibility that Cerebrolysin, a mixture of several neurotrophic factors, has some neuroprotective effects on whole body hyperthermia (WBH) induced breakdown of the blood-brain barrier (BBB), blood-CSF barrier (BCSFB), brain edema formation and neuropathology were examined in a rat model. Rats subjected to a 4 h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator exhibited profound increases in BBB and BCSFB permeability to Evans blue and radioiodine tracers compared to controls. Hippocampus, caudate nucleus, thalamus and hypothalamus exhibited pronounced increase in water content and brain pathology following 4 h heat stress. Pretreatment with Cerebrolysin (1, 2 or 5 mL/kg i.v.) 24 h before WBH significantly attenuated breakdown of the BBB or BCSFB and brain edema formation. This effect was dose dependent. Interestingly, the cell and tissue injury following WBH in cerebrolysin-treated groups were also considerably reduced. These novel observations suggest that cerebrolysin can attenuate WBH induced BBB and BCSFB damage resulting in neuroprotection.

  9. Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats.

    Science.gov (United States)

    Wang, Zhi; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2013-11-01

    Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

  10. Effects of different types of music on neuronal apoptosis of hippocampus of brain tissue of aged rats%不同类型音乐对老年大鼠脑组织海马区神经细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    何颖; 李淑梅; 马洪喜

    2014-01-01

    Objective:To explore the effects of different types of music on Caspase-3 and Livin expression levels of the hippocampus of brain tissue of aged rats.Methods: Healthly elderly male Wistar rats 40 were randomly divided into :control group , Mozart music group ,Liangzhu music group and rock music group ,n=10;water maze training every morning while music intervention 2 h,afternoon pure music intervention 2 h,continuous 7 d,the eighth days ,the rats were sacrificed and taking blood and brain tissue ,by ELISA in serum and brain tissue Caspase-3 and Livin protein contents change;using immunohistochemistry assay in rat brain tissue Caspase-3 and Livin protein levels;real-time PCR detection of rat brain tissue changes in gene level of Caspase-3 and Livin.Results:Compared with the control group ,Mozart music group ,Liangzhu music rats the protein content ,protein level and gene level of Caspase-3 of serum and brain tissue were lower statistically significant ( P0.05 );while rock music group the protein content,protein level and gene level of Caspase-3 and Livin of brain tissue were not significantly difference (P>0.05).Conclusion:Mozart music group and Liangzhu music group by reducing serum and brain tissue Caspase -3 and increased Livin , to inhibit the apoptosis of the body′s nerve cells,which play a neuroprotective effect;the rock music group in the present study ineffective.%目的:探讨不同类型音乐对老年大鼠脑组织海马区Caspase-3和Livin表达水平的影响。方法:取健康老年雄性Wistar大鼠40只,随机分为:空白对照组、莫扎特音乐组、梁祝音乐组和摇滚音乐组,每组各10只;每天上午水迷宫训练同时音乐干预2 h,下午单纯音乐干预2 h,连续7天,第8天处死大鼠取血液及脑组织,采用ELISA检测大鼠血清及脑组织中Caspase-3和Livin蛋白含量的变化水平;采用免疫组织化学法检测大鼠脑组织海马区中Caspase-3和Livin蛋白表达水平;采用实

  11. Analysis of the protein network of cholesterol homeostasis in different brain regions: an age and sex dependent perspective.

    Science.gov (United States)

    Segatto, Marco; Di Giovanni, Annalaura; Marino, Maria; Pallottini, Valentina

    2013-07-01

    Although a great knowledge about the patho-physiological roles of cholesterol metabolism perturbation in several organs has been reached, scarce information is available on the regulation of cholesterol homeostasis in the brain where this lipid is involved in the maintenance of several of neuronal processes. Currently, no study is available in literature dealing how and if sex and age may modulate the major proteins involved in the regulatory network of cholesterol levels in different brain regions. Here, we investigated the behavior of 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) and low-density lipoprotein receptor (LDLr) in adult (3-month-old) and aged (12-month-old) male and female rats. The analyses were performed in four different brain regions: cortex, brain stem, hippocampus, and cerebellum which represent brain areas characterized by different neuronal cell types, metabolism, cytoarchitecture and white matter composition. The results show that in hippocampus HMGR is lower (30%) in adult female rats than in age-matched males. Differences in LDLr expression are also observable in old females with respect to age-matched males: the protein levels increase (40%) in hippocampus and decrease (20%) in cortex, displaying different mechanisms of regulation. The mechanism underlying the observed modifications are ascribable to Insig-1 and SREBP-1 modulation. The obtained data demonstrate that age- and sex-related differences in cholesterol homeostasis maintenance exist among brain regions, such as the hippocampus and the prefrontal cortex, important for learning, memory and affection. Some of these differences could be at the root of marked gender disparities observed in clinical disease incidence, manifestation, and prognosis.

  12. Studies on the molecular correlates of genomic stability in rat brain cells following Amalakirasayana therapy.

    Science.gov (United States)

    Swain, Umakanta; Sindhu, Kiran Kumar; Boda, Ushasri; Pothani, Suresh; Giridharan, Nappan V; Raghunath, Manchala; Rao, Kalluri Subba

    2012-04-01

    Adult Wistar NIN (WNIN) rats (6 months old) of both sexes were orally fed Amalakirasayana at a dose of 4.5 g per kg body weight, five days in a week. The Amalakirasayana was prepared by Arya Vaidya Sala, Kottakkal, Kerala, India, which is considered as gold standard. After 3, 9 and 15 months of such therapeutic regime, rats were sacrificed and various tissues including brain were removed. Isolated cell suspensions of neurons and astroglia were prepared from the cerebral cortex. DNA damage, as a prime indicator of the status of genomic stability was measured in terms of single (SSBs) and double strand breaks (DSBs) through (a). The "comet" assay and (b). The biochemical methods utilizing the unique properties of Escherichia coli DNA polymerase I (pol I) and calf thymus terminal transferase. The results convincingly indicate that while in control animals, there was a distinct increase in DNA damage with age in neurons and astrocytes, rasayana fed animals showed significantly less DNA damage in brain cells demonstrating beneficial effects of Rasayana therapy towards maintenance of genomic stability. DNA-damage may be the proximal cause of aging and strategies to reduce the rate of aging could be based on this fact.

  13. Elemental concentration analysis in the brain of young and old Wistar rats by total reflection X-ray fluorescence spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Nuclear Instrumentation Lab.]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Physics Inst.]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria G.T. do [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nutrition Inst.; Rocha, Monica S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. of Basics and Clinic Pharmacy; Moreira, Silvana [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Civil Engineering Dept.; Martinez, Ana M.B. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. of Histology and Embryology

    2007-07-01

    It is well known that aging is associated with neurobehavioral deficits. The aging process of human brain is characterized by progressive neuronal loss. Furthermore, certain brain areas are more vulnerable to neuronal degeneration than others, reflecting an altered resistance to stress of the tissue itself and/or the lack of adequate immunological defense mechanisms in these regions. About the elemental levels in the brain, it is known that the excess ou deficiency of some elements are toxic for human healthy, being also related to several neurodegenerative diseases. In this way, the main goal of this work was to determine the elemental concentration in the hippocampus of young and old male (n = 10) and female (n = 10) Wistar rats by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). These measurements were carried out at XRF beam line at Light Synchrotron Brazilian Laboratory, Campinas, Brazil. About the results, we could observe that Al, Fe, Cu, Zn and Br levels were higher in the hippocampus of the old female rats than the young ones. On the other hand, only Cu levels were higher in the hippocampus of the old male rats than the young ones. Therefore, the aging of the hippocampus of the female rats can be characterized by an accumulate for Al, Fe, Cu, Zn and Br. The excess in these elements levels are also associated with several neurodegenerative disorders, such as Alzheimer' disease, Parkinson's disease and Huntington's disease. (author)

  14. Prognostic significance of age in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    S S Dhandapani

    2012-01-01

    Full Text Available Background: Age is a strong prognostic factor following traumatic brain injury (TBI, with discrepancies defining the critical prognostic age threshold. This study was undertaken to determine the impact of various age thresholds on outcome after TBI. Materials and Methods : The ages of patients admitted with TBI were prospectively studied in relation to mode of injury, Glasgow coma score (GCS, CT category and surgical intervention. Mortality was assessed at 1 month, and neurological outcome was assessed at 6 months. Appropriate statistical analyzes (details in article were performed. Results: Of the total 244 patients enrolled, 144 patients had severe, 38 patients had moderate and 62 patients had mild TBI, respectively. Age had significant association with grade of injury, CT category and surgical intervention (P 59 years respectively (P 40 years in all subgroups, based on GCS and surgical intervention (P < 0.05. Conclusions : In patients with TBI, age demonstrates independent association with unfavorable outcome at 6 months, in stepwise manner centered on a threshold of 40 years.

  15. Cross-activation and detraining effects of tongue exercise in aged rats.

    Science.gov (United States)

    Schaser, Allison J; Ciucci, Michelle R; Connor, Nadine P

    2016-01-15

    Voice and swallowing deficits can occur with aging. Tongue exercise paired with a swallow may be used to treat swallowing disorders, but may also benefit vocal function due to cross-system activation effects. It is unknown how exercise-based neuroplasticity contributes to behavior and maintenance following treatment. Eighty rats were used to examine behavioral parameters and changes in neurotrophins after tongue exercise paired with a swallow. Tongue forces and ultrasonic vocalizations were recorded before and after training/detraining in young and old rats. Tissue was analyzed for neurotrophin content. Results showed tongue exercise paired with a swallow was associated with increased tongue forces at all ages. Gains diminished after detraining in old rats. Age-related changes in vocalizations, neurotrophin 4 (NT4), and brain derived neurotrophic factor (BDNF) were found. Minimal cross-system activation effects were observed. Neuroplastic benefits were demonstrated with exercise in old rats through behavioral improvements and up-regulation of BDNF in the hypoglossal nucleus. Tongue exercise paired with a swallow should be developed, studied, and optimized in human clinical research to treat swallowing and voice disorders in elderly people.

  16. Advanced BrainAGE in older adults with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2013-12-01

    Full Text Available Aging alters brain structure and function and diabetes mellitus (DM may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs. The Brain Age Gap Estimation (i.e., BrainAGE score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM completed an MRI at 3T, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001, whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034, whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor (TNFα levels, lower verbal fluency scores and more severe depression. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019 and increased fasting blood glucose levels (r = 0.34, p = 0.025. In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM.

  17. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  18. Properties of Opiate-Receptor Binding in Rat Brain

    Science.gov (United States)

    Pert, Candace B.; Snyder, Solomon H.

    1973-01-01

    [3H]Naloxone, a potent opiate antagonist, binds stereospecifically to opiate-receptor sites in rat-brain tissue. The binding is time, temperature, and pH dependent and saturable with respect to [3H]naloxone and tissue concentration. The [3H]naloxone-receptor complex formation is bimolecular with a dissociation constant of 20 nM. 15 Opiate agonists and antagonists compete for the same receptors, whose density is 30 pmol/g. Potencies of opiates and their antagonists in displacing [3H]naloxone binding parallel their pharmacological potencies. PMID:4525427

  19. Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.

    Science.gov (United States)

    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.

  20. Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

    Energy Technology Data Exchange (ETDEWEB)

    Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

    1998-03-01

    Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

  1. Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.

    Science.gov (United States)

    Ledreux, Aurélie; Wang, Xiuzhe; Schultzberg, Marianne; Granholm, Ann-Charlotte; Freeman, Linnea R

    2016-10-01

    High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats. Young and Aged male Fisher 344 rats were fed a HFHC diet or a normal control diet for 6 months. All animals underwent cognitive testing for 12days in a water radial arm maze to assess spatial and working reference memory. Hippocampal tissue was analyzed by immunohistochemistry for structural changes and inflammation, and Western blot analysis. Young and Aged rats fed the HFHC diet exhibited worse performance on a spatial working memory task. They also exhibited significant reduction of NeuN and calbindin-D28k immunoreactivity as well as an increased activation of microglial cells in the hippocampal formation. Western blot analysis of the hippocampus showed higher levels of p-Tau S202/T205 and T231 in Aged HFHC rats, suggesting abnormal phosphorylation of Tau protein following the HFHC diet exposure. This work demonstrates HFHC diet-induced cognitive impairment with aging and a link between high fat diet consumption and pathological markers of Alzheimer's disease.

  2. [Neurotoxic effect of toluene on background of prenatal hypoxic brain damage to white rats].

    Science.gov (United States)

    Vokina, V A; Sosedova, L M; Rukavishnikov, V S; Iakimova, N L; Lizarev, A V

    2014-01-01

    Comparative study covered influence of toluene on behavioral parameters, cognitive abilities and brain bioelectric activity in white rats with normal embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day 13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4 weeks). After the exposure, the animals were estimated for individual and intraspecific behaviour in "open fields and "resident-intruder" tests, for cognitive abilities in "radial maze" training, EEG with visual and auditory evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be burdening factor and to influence consequences of toluene intoxication.

  3. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    Science.gov (United States)

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  4. Microglial cell dysregulation in Brain Aging and Neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Rommy eVon Bernhardi

    2015-07-01

    Full Text Available Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergo phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD. We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide secretion in microglia from young mice, induction of reactive oxygen species (ROS predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in a reduction of protective activation and a facilitation of cytotoxic activation of microglia, resulting in the

  5. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    Science.gov (United States)

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  6. Distribution of the mRNA for protein phosphatase T in rat brain

    NARCIS (Netherlands)

    Becker, W; Buttini, M; Limonta, S; Boddeke, H; Joost, HG

    1996-01-01

    We have recently cloned a novel protein serine/threonine phosphatase (PPT) from rat mRNA which is predominantly expressed in the brain (Becker et al., J. Biol. Chem., 269 (1994) 22586-22592). In the present study, the regional distribution of PPT mRNA in the brain of adult rats was characterized by

  7. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  8. Role of stanniocalcin1 in brain injury of coal-burning-borne fluorosis rats

    Institute of Scientific and Technical Information of China (English)

    陈旭义

    2013-01-01

    Objective To observe the change of stanniocalcin 1(STC1) and calcium content in brain of coal-burning-borne fluorosis rats,and to explore the role of STC1 in brain injury of coal-burning-borne fluorosis.Methods Twenty four male SD rats were randomly divided into control,low,medium,

  9. Age-related changes of task-specific brain activity in normal aging.

    Science.gov (United States)

    Ho, Ming-Chung; Chou, Chia-Yi; Huang, Chin-Fei; Lin, Yu-Te; Shih, Ching-Sen; Han, Shiang-Yi; Shen, Ming-Hsun; Chen, Tsung-Ching; Liang, Chi-lin; Lu, Ming-Chi; Liu, Chia-Ju

    2012-01-17

    An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices.

  10. Late behavioural and neuropathological effects of local brain irradiation in the rat.

    Science.gov (United States)

    Hodges, H; Katzung, N; Sowinski, P; Hopewell, J W; Wilkinson, J H; Bywaters, T; Rezvani, M

    1998-03-01

    The delayed consequences of radiation damage on learning and memory in rats were assessed over a period of 44 weeks, commencing 26 weeks after local irradiation of the brain with single doses of X-rays. Doses were set at levels known to produce vascular changes alone (20 Gy) or vascular changes followed by necrosis (25 Gy). Following T-maze training, 29 weeks after irradiation, irradiated and sham control groups performed equally well on the forced choice alternation task. When tested 35 weeks after irradiation, treated rats achieved a much lower percentage of correct choices than controls in T-maze alternation, with no difference between the two irradiated groups. At 38-40 weeks after irradiation, rats receiving both doses showed marked deficits in water maze place learning compared with age-matched controls; performance was more adversely affected by the higher dose. The extent of impairment was equivalent in the two groups of rats irradiated with 25 Gy, those trained or not previously trained in the T-maze, suggesting that water maze acquisition deficits were not influenced by prior experience in a different spatial task. In contrast to water maze acquisition, rats irradiated with 20 Gy showed no deficits in working memory assessed in the water maze 44 weeks after irradiation, whereas rats receiving 25 Gy showed substantial impairment. Rats receiving 25 Gy irradiation showed marked necrosis of the fimbria and degeneration of the corpus callosum, damage to the callosum occurring in animals examined histologically 46 weeks after irradiation, but in only a third of the animals examined at 41 weeks. However, there was no evidence of white matter necrosis in rats irradiated with 20 Gy, examined 46 weeks after irradiation. These findings demonstrated that local cranial irradiation with single doses of 20 and 25 Gy of X-rays produced delayed impairment of spatial learning and working memory in the rat. The extent of these deficits appears to be task- and dose

  11. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  12. Oral branched-chain amino acid supplements that reduce brain serotonin during exercise in rats also lower brain catecholamines.

    Science.gov (United States)

    Choi, Sujean; Disilvio, Briana; Fernstrom, Madelyn H; Fernstrom, John D

    2013-11-01

    Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Sedentary and exercising rats received BCAA or vehicle orally; tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis rates were measured 1 h later in brain. BCAA reduced brain tryptophan and tyrosine concentrations, and serotonin and catecholamine synthesis. These reductions in tyrosine concentrations and catecholamine synthesis, but not tryptophan or serotonin synthesis, could be prevented by co-administering tyrosine with BCAA. Complete essential amino acid mixtures, used to maintain or build muscle mass, were also studied, and produced different effects on brain tryptophan and tyrosine concentrations and serotonin and catecholamine synthesis. Since pharmacologically increasing brain catecholamine function improves physical performance, the finding that BCAA reduce catecholamine synthesis may explain why this treatment does not enhance physical performance in humans, despite reducing serotonin synthesis. If so, adding tyrosine to BCAA supplements might allow a positive action on performance to emerge.

  13. Effect of cytisine on some brain and hepatic biochemical parameters in spontaneously hypertensive rats.

    Science.gov (United States)

    Simeonova, Rumyana; Vitcheva, Vessela; Mitcheva, Mitka

    2010-03-01

    Tobacco smoking is a risk factor for variety of cardio-vascular diseases, such as hypertension, myocardial infarction, stroke and many others. It is of great importance for hypertensive patients to stop smoking. One of the medicines widely used for smoking cessation in Bulgaria is the original Bulgarian product Tabex®, which is developed on the basis of natural plant alkaloid cytisine. The aim of the following study was to ivestigate the effects of cytisine on some brain and hepatic biochemical parameters in spontaneously hypertensive rats (SHR), an widely used rodent model for human essential hypertension, and to compare the obtained results with their age-matched normotensive controls Wistar Kyoto (WKY). Multiple cytisine administration did not affect the activity of ethylmorphine-N-demethylase (EMND) and anylinehydroxylase (AH), as well as the quantity of cytochrome P 450, nor in WKY neither in SHR In the liver cytisine increased the MDA quantity both in SHR and in WKY, by 25% (p<0.05) and by 29% (p<0.05) respectively, while the GSH level was not significantly changed by the compound in both strains. In contrast, on the brain level, cytisine administration to SHR caused more prominent toxicity, resulted in GSH depletion and increased MDA quantity, while in WKY strain did not exert any toxicity. Cytisine did not significantly affect ALAT and ASAT activity in both strains. In conclusion, the results of our study suggest higher brain toxicity of cytisine in spontaneously hypertensive rats, that might be due to their pathophysiological characteristics.

  14. Prior infection exacerbates postoperative cognitive dysfunction in aged rats

    NARCIS (Netherlands)

    Hovens, Iris B.; van Leeuwen, Barbara L.; Nyakas, Csaba; Heineman, Erik; van der Zee, Eddy A.; Schoemaker, Regien G.

    2015-01-01

    Older patients may experience persisting postoperative cognitive dysfunction (POCD), which is considered to largely depend on surgery-induced (neuro) inflammation. We hypothesize that inflammatory events before surgery could predispose patients to POCD. When part of our aged rats developed Mycoplasm

  15. Exercise Training suppresses vascular fibrosis in aging obesity induced rats

    Science.gov (United States)

    Kim, Shin Young; Lee, Jin

    2014-01-01

    [Purpose] The aim of this study was to investigate the effects of exercise training (ET) on vascular fibrosis in aging model rats with diet-induced obesity. [Methods] Twenty-four male Sprague-Dawley rats were divided into 3 groups: Aging control (A-C), A-C with high fat diet (AHF), AHF with ET (AHF + ET). Aging was induced by D-galactose (D-gal) and obesity was induced by HFD (60% fat) for 9 weeks. The experimental rats performed swimming (60 min/day, 5 days/week) for 8 weeks. All rat aorta samples were harvested for RT-PCR and morphologic analyses. [Results] The exercise training significantly decreased levels of AT-1, TGF-ß and Coll-1 gene expression compared to AHF group. The AHF + ET group showed a reduced collagen accumulation in the aorta media compared to AHF group. [Conclusion] These results suggest that ET could protect the aging obesity aorta against down-regulation of fibrotic factors (AT-1, TGF-ß and Coll-1 gene) and fibrosis by inhibition of collagen accumulation in the aorta media. PMID:25566453

  16. Spontaneous Object Recognition Memory in Aged Rats: Complexity versus Similarity

    Science.gov (United States)

    Gamiz, Fernando; Gallo, Milagros

    2012-01-01

    Previous work on the effect of aging on spontaneous object recognition (SOR) memory tasks in rats has yielded controversial results. Although the results at long-retention intervals are consistent, conflicting results have been reported at shorter delays. We have assessed the potential relevance of the type of object used in the performance of…

  17. Surgery-induced behavioral changes in aged rats

    NARCIS (Netherlands)

    Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Heineman, Erik; Nyakas, Csaba; van Leeuwen, Barbara L.; Humpel, Christian

    2013-01-01

    Elderly patients may experience impairments in cognition or mood following surgery. To study the development and underlying mechanisms of these postoperative behavioral changes, young (3 months) and aged (18-20 months) male rats were subjected to abdominal surgery followed by behavioral testing duri

  18. Neuroprotective effect ofShenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying-min Cai; Yong Zhang; Peng-bo Zhang; Lu-ming Zhen; Xiao-ju Sun; Zhi-ling Wang; Ren-yan Xu; Rong-liang Xue

    2016-01-01

    Shenqi Fuzheng injection is extracted from the Chinese herbsRadix Astragali andRadix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20–22 months) were divided into three groups: sham, model, and treatment.Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca2+levels, lower ac-tivities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our ifndings indicate thatShenqi Fuzheng injec-tion exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca2+ accumulation.

  19. Potential urinary aging markers of 20-month-old rats

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    Xundou Li

    2016-06-01

    Full Text Available Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old and old rats (20 months old; nine in each group were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2, P < 0.05 and identification in each rat of the high-abundance group, 33 proteins were found to be changed (15 increased and 18 decreased in old rats. By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group, eight proteins showed consistent changes in all rats of the groups; two of these proteins are also altered in the urinary proteome of aging humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60% altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs.

  20. DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

    Institute of Scientific and Technical Information of China (English)

    YING XIAO; LING WANG; RUO-JUN XU; ZHEN-YU CHEN

    2006-01-01

    Objective To examine the effect of docosahexaenoic acid (DHA) deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain. DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze (MWM) was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain. The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Conclusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

  1. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  2. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  3. NO-tryptophan: a new small molecule located in the rat brain

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    A. Mangas

    2016-09-01

    Full Text Available A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W with good affinity (10-9 M and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. 

  4. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

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    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  5. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

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    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  6. Anticancer and antioxidant properties of terpinolene in rat brain cells.

    Science.gov (United States)

    Aydin, Elanur; Türkez, Hasan; Taşdemir, Sener

    2013-09-01

    Terpinolene (TPO) is a natural monoterpene present in essential oils of many aromatic plant species. Although various biological activities of TPO have been demonstrated, its neurotoxicity has never been explored. In this in vitro study we investigated TPO's antiproliferative and/or cytotoxic properties using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic damage potential using the single-cell gel electrophoresis (SCGE), and oxidative effects through total antioxidant capacity (TAC) and total oxidative stress (TOS) in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(-1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1) it increased TOS in both cell types. Our findings clearly demonstrate that TPO is a potent antiproliferative agent for brain tumour cells and may have potential as an anticancer agent, which needs to be further studied.

  7. Brain choline acetyltransferase and muscarinic receptor sites, brain and liver cholinesterases in precocial Acomys cahirinus and altricial rat during post-natal development.

    Science.gov (United States)

    Michalek, H; Pintor, A; Fortuna, S; Bisso, G M

    1988-01-01

    Brain choline acetyltransferase, acetylcholinesterase with its molecular forms, and muscarinic receptor sites, as well as liver total cholinesterases were evaluated during the first postnatal month in pups of a precocial (Acomys cahirinus) and altricial (rat) murid species. At birth the levels of brain cholinergic markers were higher in the Acomys than in the rat, but in adulthood the differences were smaller or even reversed. The postnatal increase up in the markers to weaning was considerably more pronounced in the rat. However, substantial variations in the patterns of development of the three cholinergic markers within and between species were observed. Liver cholinesterases were considerably higher in Acomys than in rats at all ages investigated. These and literature data are discussed in relation to postnatal, post-conception and post-organogenesis age of pups belonging to the two species. The variability of the ontogenetic patterns between the enzymes suggests that there is some biological control of individual rates of maturation and that it is necessary to be careful in broadly interpreting growth patterns across organs within the same species and across species.

  8. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was exa

  9. Genetic Determinants of Cognitive Function and Age-Related Brain Changes

    NARCIS (Netherlands)

    M. Schuur (Maaike)

    2010-01-01

    textabstractThe brain is by far the most complicated structure of the human being, and its malfunction is characterized by various degrees and types of morbidity. Several brain functions deteriorate with increasing age during life. Cognitive decline and age-related brain pathology are common in the

  10. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

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    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  11. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  12. Kappa opioid receptors stimulate phosphoinositide turnover in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Periyasamy, S.; Hoss, W. (Univ. of Toledo, OH (USA))

    1990-01-01

    The effects of various subtype-selective opioid agonists and antagonists on the phosphoinositide (PI) turnover response were investigated in the rat brain. The {kappa}-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other {kappa}-agonists Dynorphin-A (1-13) amide, and its protected analog D(Ala){sup 2}-dynorphin-A (1-13) amide also produced a significant increase in the formation of ({sup 3}H)-IP's, whereas the {mu}-selective agonists (D-Ala{sup 2}-N-Me-Phe{sup 4}-Gly{sup 5}-ol)-enkephalin and morphine and the {delta}-selective agonist (D-Pen{sup 2,5})-enkephalin were ineffective. The increase in IP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the {kappa}-selective antagonists nor-binaltorphimine and MR 2266. The formation of IP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medullar. The results indicate that brain {kappa}- but neither {mu}- nor {delta}- receptors are coupled to the PI turnover response.

  13. Quinolinic acid induces oxidative stress in rat brain synaptosomes.

    Science.gov (United States)

    Santamaría, A; Galván-Arzate, S; Lisý, V; Ali, S F; Duhart, H M; Osorio-Rico, L; Ríos, C; St'astný, F

    2001-03-26

    The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 microM). The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 microM) and APV (250 microM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor.

  14. Selective glial vulnerability following transient global ischemia in rat brain.

    Science.gov (United States)

    Petito, C K; Olarte, J P; Roberts, B; Nowak, T S; Pulsinelli, W A

    1998-03-01

    Global cerebral ischemia selectively damages neurons, but its contribution to glial cell death is uncertain. Accordingly, adult male rats were sacrificed by perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic (PI) day 3, but minor or no damage to neurons in other regions. In situ end labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia, astrocytes, and microglia were present in control brain. Apoptotic bodies and ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p < 0.05), but were similar to controls in other regions and at other PI intervals. Most were oligodendroglia, although ISEL-positive microglia and astrocytes were also observed. These results show that oligodendroglia die rapidly after brief global ischemia and are more sensitive than neurons in certain brain regions. Their selective vulnerability to ischemia may be responsible for the delayed white matter damage following anoxia or CO poisoning or that associated with white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders of apoptotic oligonucleosomes that have been found in post-ischemic brain.

  15. Decrease in age-related tau hyperphosphorylation and cognitive improvement following vitamin D supplementation are associated with modulation of brain energy metabolism and redox state.

    Science.gov (United States)

    Briones, T L; Darwish, H

    2014-03-14

    In the present study we examined whether vitamin D supplementation can reduce age-related tau hyperphosphorylation and cognitive impairment by enhancing brain energy homeostasis and protein phosphatase 2A (PP2A) activity, and modulating the redox state. Male F344 rats aged 20 months (aged) and 6 months (young) were randomly assigned to either vitamin D supplementation or no supplementation (control). Rats were housed in pairs and the supplementation group (n=10 young and n=10 aged) received subcutaneous injections of vitamin D (1, α25-dihydroxyvitamin D3) for 21 days. Control animals (n=10 young and n=10 aged) received equal volume of normal saline and behavioral testing in the water maze started on day 14 after the initiation of vitamin D supplementation. Tau phosphorylation, markers of brain energy metabolism (ADP/ATP ratio and adenosine monophosphate-activated protein kinase) and redox state (levels of reactive oxygen species, activity of superoxide dismutase, and glutathione levels) as well as PP2A activity were measured in hippocampal tissues. Our results extended previous findings that: (1) tau phosphorylation significantly increased during aging; (2) markers of brain energy metabolism and redox state are significantly decreased in aging; and (3) aged rats demonstrated significant learning and memory impairment. More importantly, we found that age-related changes in brain energy metabolism, redox state, and cognitive function were attenuated by vitamin D supplementation. No significant differences were seen in tau hyperphosphorylation, markers of energy metabolism and redox state in the young animal groups. Our data suggest that vitamin D ameliorated the age-related tau hyperphosphorylation and cognitive decline by enhancing brain energy metabolism, redox state, and PP2A activity making it a potentially useful therapeutic option to alleviate the effects of aging.

  16. Chronic Lead Exposure and Mixed Factors of Gender×Age×Brain Regions Interactions on Dendrite Growth, Spine Maturity and NDR Kinase.

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    Yang Du

    Full Text Available NDR1/2 kinase is essential in dendrite morphology and spine formation, which is regulated by cellular Ca2+. Lead (Pb is a potent blocker of L-type calcium channel and our recent work showed Pb exposure impairs dendritic spine outgrowth in hippocampal neurons in rats. But the sensitivity of Pb-induced spine maturity with mixed factors (gender×age×brain regions remains unknown. This study aimed to systematically investigate the effect of Pb exposure on spine maturity in rat brain with three factors (gender×age×brain regions, as well as the NDR1/2 kinase expression. Sprague-Dawley rats were exposed to Pb from parturition to postnatal day 30, 60, 90, respectively. Golgi-Cox staining was used to examine spine maturity. Western blot assay was applied to measure protein expression and real-time fluorescence quantitative PCR assay was used to examine mRNA levels. The results showed chronic Pb exposure significantly decreased dendritic length and impaired spine maturity in both rat hippocampus and medial prefrontal cortex. The impairment of dendritic length induced by Pb exposure tended to adolescence > adulthood, hippocampus > medial prefrontal cortex and female > male. Pb exposure induced significant damage in spine maturity during adolescence and early adult while little damage during adult in male rat brain and female medial prefrontal cortex. Besides, there was sustained impairment from adolescence to adulthood in female hippocampus. Interestingly, impairment of spine maturity followed by Pb exposure was correlated with NDR1/2 kinase. The reduction of NDR1/2 kinase protein expression after Pb exposure was similar to the result of spine maturity. In addition, NDR2 and their substrate Rabin3 mRNA levels were significantly decreased by Pb exposure in developmental rat brain. Taken together, Pb exposure impaired dendrite growth and maturity which was subject to gender×age×brain regions effects and related to NDR1/2 signal expression.

  17. Dietary choline deprivation impairs rat brain mitochondrial function and behavioral phenotype.

    Science.gov (United States)

    Pacelli, Consiglia; Coluccia, Addolorata; Grattagliano, Ignazio; Cocco, Tiziana; Petrosillo, Giuseppe; Paradies, Giuseppe; De Nitto, Emanuele; Massaro, Antonio; Persichella, Michele; Borracci, Pietro; Portincasa, Piero; Carratù, Maria Rosaria

    2010-06-01

    Dietary choline deprivation (CD) is associated with behavioral changes, but mechanisms underlying these detrimental effects are not well characterized. For instance, no literature data are available concerning the CD effects on brain mitochondrial function related to impairment in cognition. Therefore, we investigated brain mitochondrial function and redox status in male Wistar rats fed a CD diet for 28 d. Moreover, the CD behavioral phenotype was characterized. Compared with rats fed a control diet (CTRL), CD rats showed lower NAD-dependent mitochondrial state III and state IV respiration, 40% lower complex I activity, and significantly higher reactive oxygen species production. Total glutathione was oxidatively consumed more in CD than in CTRL rats and the rate of protein oxidation was 40% higher in CD than in CTRL rats, reflecting an oxidative stress condition. The mitochondrial concentrations of cardiolipin, a phospholipid required for optimal activity of complex I, was 20% lower in CD rats than in CTRL rats. Compared with CTRL rats, the behavioral phenotype of CD rats was characterized by impairment in motor coordination and motor learning assessed with the rotarod/accelerod test. Furthermore, compared with CTRL rats, CD rats were less capable of learning the active avoidance task and the number of attempts they made to avoid foot shock was fewer. The results suggest that CD-induced dysfunction in brain mitochondria may be responsible for impairment in cognition and underline that, similar to the liver, the brain also needs an adequate choline supply for its normal functioning.

  18. 脑血流低灌注老龄大鼠中脑皮质血流的改变与血清总胆固醇和高密度脂蛋白的动态变化%Dynamic changes of cortical blood flow and serum total cholesterol and high density lipoprotein in brains of aging rat during cerebral hypoperfusion

    Institute of Scientific and Technical Information of China (English)

    王林辉; 田茗源; 滕志朋; 王晨; 李昱

    2012-01-01

    目的:通过建立脑血流低灌注模型,观察老龄大鼠脑血流的变化以及在脑血流低灌注下血清中总胆固醇(Total cholesterol,TC)和高密度脂蛋白(High density lipoprotein,HDL)的动态变化.方法:采用持久性双侧颈总动脉结扎法(2Vo)致老龄大鼠脑血流灌注不足,测定术后7、14、21、28d大鼠脑皮质血流;检测、比较术后不同时间段大鼠血清中TC和HDL浓度差异.结果:术后第14天大鼠脑颞区血流出现明显减少;术后21、28d大鼠脑局部皮质血管有再生侧支形成,大鼠脑颞区血流仍未恢复;术后第14天血清中HDL、TC含量明显高于假手术组(P<0.05),随着缺血时间延长,又逐渐降低.结论:血清TC和HDL浓度在脑缺血灌注不足的不同时间段经历了先增强后减弱的动态变化,提示脑血流低灌注老龄大鼠因大脑血流灌注不足可出现体内胆固醇代谢失衡并出现应激调节现象.%Objective: To investigate the change of cortical blood flow and the dynamic changes of serum total cholesterol(TC ) and high density lipoprotein(HDL) in brains of aging rat during cerebral ischemic injury. Methods:The model of aging rats with cerebral hy-poperfusion was successfully constructed by persistent bilateral common carotid artery ligation(2V0). The cortical blood flow and the concentration of serum TC and HDL at different time points were determined and compared. Results: Compared with the sham-operated group,the temporal blood flow was significantly decreased in 14 d group. But the collateral vessels were gradually regenerated and formed in local brain,while the temporal blood flow was restored in 21 d and 28 d group. The concentration of HDL and TC was significantly higher in 14 d group than in the sham-operated group (P<0.05), and both of them were decreased with the extention of ischemia time. Conclusions:The serum TC and HDL concentration undergo dynamic changes-increasing first and then decreasing during the process

  19. Prion protein accumulation in lipid rafts of mouse aging brain.

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    Federica Agostini

    Full Text Available The cellular form of the prion protein (PrP(C is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C. In old mice, this change favors PrP(C accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C translocation into detergent-resistant membranes (DRMs, we looked at PrP(C compartmentalization in hippocampi from acid sphingomyelinase (ASM knockout (KO mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.

  20. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Christian Gaser

    Full Text Available Alzheimer's disease (AD, the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI-based biomarker that predicts the individual progression of mild cognitive impairment (MCI to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%. The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF. With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]. Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  1. Oxidative stress of brain and liver is increased by Wi-Fi (2.45GHz) exposure of rats during pregnancy and the development of newborns.

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    Çelik, Ömer; Kahya, Mehmet Cemal; Nazıroğlu, Mustafa

    2016-09-01

    An excessive production of reactive oxygen substances (ROS) and reduced antioxidant defence systems resulting from electromagnetic radiation (EMR) exposure may lead to oxidative brain and liver damage and degradation of membranes during pregnancy and development of rat pups. We aimed to investigate the effects of Wi-Fi-induced EMR on the brain and liver antioxidant redox systems in the rat during pregnancy and development. Sixteen pregnant rats and their 48 newborns were equally divided into control and EMR groups. The EMR groups were exposed to 2.45GHz EMR (1h/day for 5 days/week) from pregnancy to 3 weeks of age. Brain cortex and liver samples were taken from the newborns between the first and third weeks. In the EMR groups, lipid peroxidation levels in the brain and liver were increased following EMR exposure; however, the glutathione peroxidase (GSH-Px) activity, and vitamin A, vitamin E and β-carotene concentrations were decreased in the brain and liver. Glutathione (GSH) and vitamin C concentrations in the brain were also lower in the EMR groups than in the controls; however, their concentrations did not change in the liver. In conclusion, Wi-Fi-induced oxidative stress in the brain and liver of developing rats was the result of reduced GSH-Px, GSH and antioxidant vitamin concentrations. Moreover, the brain seemed to be more sensitive to oxidative injury compared to the liver in the development of newborns.

  2. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    Science.gov (United States)

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future.

  3. Dedifferentiation of emotion regulation strategies in the aging brain.

    Science.gov (United States)

    Martins, Bruna; Ponzio, Allison; Velasco, Ricardo; Kaplan, Jonas; Mather, Mara

    2015-06-01

    Different emotion regulation strategies are distinctly represented in the brains of younger adults. Decreasing a reaction to a negative situation by reinterpreting it (reappraisal) relies on cognitive control regions in the prefrontal cortex, while distracting away from a stressor involves more posterior medial structures. In this study, we used Multi-Voxel pattern analyses (MVPA) to examine whether reappraisal and distraction strategies have distinct representations in the older adult brain, or whether emotion regulation strategies become more dedifferentiated in later life. MVPA better differentiated the two emotion regulation strategies for younger adults than for older adults, and revealed the greatest age-related differences in differentiation in the posterior medial cortex (PMC). Univariate analyses revealed equal PMC recruitment across strategies for older adults, but greater activity during distraction than reappraisal for younger adults. The PMC is central to self-focused processing, and thus our findings are consistent with the possibility that focusing on the self may be a default mechanism across emotion regulation strategies for older people.

  4. Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

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    Lovatel, Gisele Agustini; Elsner, Viviane Rostirola; Bertoldi, Karine; Vanzella, Cláudia; Moysés, Felipe Dos Santos; Vizuete, Adriana; Spindler, Christiano; Cechinel, Laura Reck; Netto, Carlos Alexandre; Muotri, Alysson Renato; Siqueira, Ionara Rodrigues

    2013-03-01

    It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-β and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.

  5. The effects of ecstasy (MDMA on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals.

    Directory of Open Access Journals (Sweden)

    Anne Klomp

    Full Text Available RATIONALE AND OBJECTIVE: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. METHODS: 5-HT transporter (SERT densities in the frontal cortex and midbrain were assessed with [(123I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain, and late-exposed users (age-at-first exposure 18-36 years; mature brain. In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent rats and late-exposed (adult rats using the same radioligand. RESULTS: On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain exposed ecstasy users, whereas this was only 0.3% in late (mature brain exposed users (p=0.007. No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01 was observed as well, however only in the frontal cortex. CONCLUSIONS: These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.

  6. [POLYPEPTIDES INFLUENCE ON TISSUE CELL CULTURES REGENERATION OF VARIOUS AGE RATS].

    Science.gov (United States)

    Ryzhak, A P; Chalisova, N I; Lin'kova, N S; Khalimov, R I; Ryzhak, G A; Zhekalov, A N

    2015-01-01

    A comparative study of polypeptides extracted from the tissues of calves: Cortexin (from brain cortex), Epinorm (from pineal gland), Ventvil (from liver), Prostatilen (from prostate), Thymalin (from thymus), Chelohart (from heart), Chondrolux (from cartilage) on the relevant organotypic tissue cultures of young and old rats, in concentration 0,01-100 ng/ml was performed. Polypeptides specifically stimulated "young" and "old" cell cultures growth in concentration 20-50 ng/ml. This effect correlates with increasing of PCNA and decreasing of p53 expression in brain cortex, pineal gland, liver, prostate, heart, cartilage. Moreover, Thymalin activated CD5, CD20 expression--markers of B-cells differentiation. These data show that polypeptides isolated from different tissues have selective molecular activity on the regeneration of suitable tissues in aging.

  7. Localization and labeling of rat brain in MR image based on Paxinos-Watson atlas

    Science.gov (United States)

    Cao, Jie; Cai, Chao; Ding, Mingyue; Zhou, Chengping

    2006-03-01

    Localization and labeling of function regions in brain is an important topic in experimental brain sciences because the huge amount of data collected by neuroscientists will become meaningless if we cannot give them a precise description of their locations. In this paper, we proposed a localization and labelling method of 3D MR image of rat brain based on Paxinos-Watson atlas. Our objective is to use the specific atlas to accomplish localization and labeling of specified tissue of interest (TOI) to mimic a veteran expert such that invisible or unclear anatomic function regions in the MR images of rat brain can be automatically identified and marked. We proposed a multi-step method to locate and label the TOIs from the MR image of rat brain. Firstly, pre-processing. It aims at the digitization and 3D reconstruction of the atlas and MRI of rat brain. Secondly, two-step registration. The global registration is to eliminate the big misalign and section angle offset as well as the scale between the MRI and atlas. We can choose some unambiguous and characteristic points manually, and based on these correspondences a coarse registration is obtained using affine model. The local registration is to address individual variability of rat brain that can be performed by using Snake model. Thirdly, post-processing. The goal is to locate and label the TOIs in the selected MR image of rat brain slice guided by well-registered atlas. The experiments demonstrated the feasibility of our method.

  8. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  9. Sex Differences in Serotonin 1 Receptor Binding in Rat Brain

    Science.gov (United States)

    Fischette, Christine T.; Biegon, Anat; McEwen, Bruce S.

    1983-10-01

    Male and female rats exhibit sex differences in binding by serotonin 1 receptors in discrete areas of the brain, some of which have been implicated in the control of ovulation and of gonadotropin release. The sex-specific changes in binding, which occur in response to the same hormonal (estrogenic) stimulus, are due to changes in the number of binding sites. Castration alone also affects the number of binding sites in certain areas. The results lead to the conclusion that peripheral hormones modulate binding by serotonin 1 receptors. The status of the serotonin receptor system may affect the reproductive capacity of an organism and may be related to sex-linked emotional disturbances in humans.

  10. Label-free dopamine imaging in live rat brain slices.

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    Sarkar, Bidyut; Banerjee, Arkarup; Das, Anand Kant; Nag, Suman; Kaushalya, Sanjeev Kumar; Tripathy, Umakanta; Shameem, Mohammad; Shukla, Shubha; Maiti, Sudipta

    2014-05-21

    Dopaminergic neurotransmission has been investigated extensively, yet direct optical probing of dopamine has not been possible in live cells. Here we image intracellular dopamine with sub-micrometer three-dimensional resolution by harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon excitation with visible light (540 nm) in conjunction with a non-epifluorescent detection scheme is used to circumvent the UV toxicity and the UV transmission problems. The method is established by imaging dopamine in a dopaminergic cell line and in control cells (glia), and is validated by mass spectrometry. We further show that individual dopamine vesicles/vesicular clusters can be imaged in cultured rat brain slices, thereby providing a direct visualization of the intracellular events preceding dopamine release induced by depolarization or amphetamine exposure. Our technique opens up a previously inaccessible mid-ultraviolet spectral regime (excitation ~270 nm, emission free imaging of native molecules in live tissue.

  11. Antioxidant effects of calcium antagonists in rat brain homogenates.

    Science.gov (United States)

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T

    2000-06-01

    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  12. Regional protein synthesis in rat brain following acute hemispheric ischemia.

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    Dienel, G A; Pulsinelli, W A; Duffy, T E

    1980-11-01

    Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.

  13. Benznidazole levels in blood vary with age in rats

    Directory of Open Access Journals (Sweden)

    Romina Fernanda Bulffer

    2011-05-01

    Full Text Available Benznidazole (Bz exhibits toxic side effects in animal studies and clinical use. Reductive metabolism of Bz in liver microsomes modulates the duration of its chemotherapeutic effect and its toxicity. The rate of this metabolism depends on age and is less intense in newborns and youngsters than in adults. In the present study, we determined Bz blood levels in rats of different ages that received Bz intragastrically (100 mg/kg. We developed and validated a high-pressure liquid chromatography with UV detector method for determination of Bz levels in whole blood. Bz levels were significantly higher and persisted for longer periods of time in the blood of young rats when compared to that of adult animals.

  14. Trajectories of brain aging in middle-aged and older adults: regional and individual differences.

    Science.gov (United States)

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M; Kennedy, Kristen M; Lindenberger, Ulman

    2010-06-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital-frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial-temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEepsilon4 allele exhibited declines not noted in the whole sample.

  15. Effects of Atorvastatin on the Hypertension-Induced Oxidative Stress in the Rat Brain

    OpenAIRE

    Mohammadi, Mohammad Taghi; Amini, Reza; Jahanbakhsh, Zahra; Shekarforoush, Shahnaz

    2013-01-01

    Background: It is well known that the development of brain oxidative stress is one of the most serious complications of arterial hypertension that evokes brain tissue damage. The aim of this study was to examine the effects of atorvastatin treatment (20 mg/kg/day), as an antioxidant, to prevent the brain tissue oxidative stress in the hypertensive (HTN) rats. Methods: Experiments were performed in four groups of rats (n = 5 each group): sham, sham-treated, HTN and HTN treated. Rats were made ...

  16. Adenovirally Delivered Brain-derived Neurotrophic Factor to Rat Retina

    Institute of Scientific and Technical Information of China (English)

    Xu Hou; Dan Hu; Yannian Hui

    2004-01-01

    Purpose: To study the expression of brain-derived neurotrophic factor (BDNF) in the rat retina delivered by adenovirus.Methods: Adenovirus with BDNF gene was injected into the vitreous. Gene expression was detected by immunofluorescence staining, and quantitative analysis was performed after injury and transfection by Enzyme-linked immunosorbent assay (ELISA).Results: The positive cells can be seen on the 3rd day and last 4 weeks by immunofluorescence staining. Positive cells in the control group were fewer than those in the transfection group or the fluorescence intensity was lower at every time point. Quantitative analysis showed that the expression of BDNF groups was higher than that of the control group at every time point(P < 0.01 ), and that of the injured group without transfection was higher than that of the control group on the 3rd day and the 7th day (P < 0.01 ).Conclusion: Efficient and stable transfer of BDNF gene could be achieved by adenovirus delivery into the retina of rats. Injury can promote the expression of BDNF in early period.

  17. [Pineal gland glutathione peroxidase activity in rats and its age-associated change].

    Science.gov (United States)

    Razygraev, A V

    2010-01-01

    Glutathione peroxidase activity has been studied in the pineal gland (epiphysis) of young and aging female Wistar rats (2-4 and 17-19 month old). For comparison the same activity was studied in the pyramids of medulla oblongata and in the olfactory tubercle. These two brain structures represent white and gray matter respectively. The determination of the activity was performed with H2O2 as a substrate and with 5,5'-dithio-bis-(2-nitrobenzoic acid) for estimation of the decrease of restored form of glutathione concentration. The glutathione peroxidase activity was higher in the pineal gland than in the brain structures used. Pineal glutathione peroxidase activities (micromole of GSH per minute per milligram of protein, M +/- m) in young and old rats were 1,52 +/- 0,07 and 1,27 +/- 0,06 respectively (prats is the age-associated decrease of the selenium content in the pineal gland. The decline found may be one of the reflections of the pineal gland functional involution.

  18. Extensive enriched environments protect old rats from the aging dependent impairment of spatial cognition, synaptic plasticity and nitric oxide production.

    Science.gov (United States)

    Lores-Arnaiz, S; Bustamante, J; Arismendi, M; Vilas, S; Paglia, N; Basso, N; Capani, F; Coirini, H; Costa, J J López; Arnaiz, M R Lores

    2006-05-15

    In aged rodents, neuronal plasticity decreases while spatial learning and working memory (WM) deficits increase. As it is well known, rats reared in enriched environments (EE) show better cognitive performances and an increased neuronal plasticity than rats reared in standard environments (SE). We hypothesized that EE could preserve the aged animals from cognitive impairment through NO dependent mechanisms of neuronal plasticity. WM performance and plasticity were measured in 27-month-old rats from EE and SE. EE animals showed a better spatial WM performance (66% increase) than SE ones. Cytosolic NOS activity was 128 and 155% higher in EE male and female rats, respectively. Mitochondrial NOS activity and expression were also significantly higher in EE male and female rats. Mitochondrial NOS protein expression was higher in brain submitochondrial membranes from EE reared rats. Complex I activity was 70-80% increased in EE as compared to SE rats. A significant increase in the area of NADPH-d reactive neurons was observed in the parietotemporal cortex and CA1 hippocampal region of EE animals.

  19. Effect of ethanol on enkephalinergic opioid system of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Belyayev, N.A.; Balakireva, N.N.; Brusov, O.S.; Panchenko, L.F.

    1983-10-13

    Specific binding of /sup 3/H-morphine and /sup 3/H-(D-Ala/sup 2/, D-Leu/sup 5/)-enkephalin (H-EN) with opiatic receptors was studied on white rats along with the content of Met- and Leu-enkephalin and the activity of enkephalinase in various brain segments after single dose (20% solution in 0.9% NaCl, IP; 1.5-4.5 g/kg body weight) and chronic injection (20% EtOH substituted for drinking water) of ethanol. The single injection of EtOH (1.5-4.5 g/kg) resulted in a depression of the specific binding of H-EN with opiate receptors. Doses of 1.5 and 2.5 g/kg led to a lower content of Leu-enkephalin in mid-brain but to an increase of Met-enkephalin; the 4.5 g/kg dose had no effect on the striatum. With chronic administration of EtOH, most of the values obtained on the experimental animals were similar to the control data. 23 references.

  20. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  1. Regional energy balance in rat brain after transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1983-05-01

    Phosphocreatine, ATP, and glucose were severely depleted, and the lactate levels were increased in the paramedian neocortex, dorsal-lateral striatum, and CA1 zone of hippocampus of rats exposed to 30 min of forebrain ischemia. Upon recirculation of the brain, phosphocreatine, ATP, and lactate concentrations recovered to control values in the paramedian neocortex and CA1 zone of hippocampus and to near-control values in the striatum. The phosphocreatine and ATP concentrations then fell and the lactate levels rose in the striatum after 6-24 h, and in the CA1 zone of hippocampus after 24-72 h. The initial recovery and subsequent delayed changes in the phosphocreatine, ATP, and lactate concentrations in the striatum and hippocampus coincided with the onset and progression of morphological injury in these brain regions. The results suggest that cells in these regions regain normal or near-normal mitochondrial function and are viable, in terms of energy production, for many hours before unknown mechanisms cause irreversible neuronal before unknown mechanisms cause irreversible neuronal injury.

  2. Rat brain aryl acylamidase: further characterization of multiple forms.

    Science.gov (United States)

    Hsu, L L; Halaris, A E; Freedman, D X

    1982-01-01

    1. Two fractions of aryl acylamidase (EC 3.5.1.13) were further separated from rat brain extracts at pH 7.5 by ammonium sulfate precipitation and Bio-Gel chromatography. 2. 1,2,3,4-Tetrahydro-beta-carboline competitively inhibited (67%) fraction-1 but slightly inhibited (13%) fraction-2. Tetrahydroharman, 6-hydroxy-tetrahydroharman and harminic acid slightly inhibited both fractions. Harmalol inhibited fraction-1 but enhanced fraction-2. 6-Methoxy-harman, 6-methoxy-harmalan and harmaline enhanced both fractions. 3. Pargyline did not affect either fraction. Methiothepin, cyproheptadine and chlorimipramine inhibited fraction-1 but stimulated fraction-2. 4. Neostigmine moderately (30%) inhibited AAA-2 but did not have any significant effect on AAA-1. 5. These results indicate that the beta-carboline compounds might play a role in regulating activity of AAA-1 and 2 in brain. 6. Both fractions might be related to serotonergic neurons but only AAA-2 might be associated with acetylcholinesterase.

  3. Are soluble and membrane-bound rat brain acetylcholinesterase different

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    Andres, C.; el Mourabit, M.; Stutz, C.; Mark, J.; Waksman, A. (Centre de Neurochimie du C.N.R.S., Strasbourg, (France))

    1990-11-01

    Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.

  4. Montefiore-Einstein Center for the Aging Brain: Preliminary Data.

    Science.gov (United States)

    Verghese, Joe; Malik, Rubina; Zwerling, Jessica

    2016-11-01

    Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one-year experience with outpatient based dementia care at the Montefiore-Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non-pharmacological treatments as appropriate, and the facilitation of access to clinical trials. The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self-identified ethnicity of patients included Caucasian (26%), African-American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one-year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians.

  5. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  6. Age-related changes of normal adult brain structure: analysed with diffusion tensor imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Chun-yan; ZHANG Jing; LI Wei

    2005-01-01

    Background It is known that the brain structure changes with normal aging. The objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging.Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups.Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

  7. Brain Metabolic Changes in Rats following Acoustic Trauma

    Science.gov (United States)

    He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

    2017-01-01

    Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine

  8. Brain lipids in rats fed a diet supplemented with hen eggs of modified lipid content

    Directory of Open Access Journals (Sweden)

    Hodžić Aida

    2012-01-01

    Full Text Available The aim of this study was to research the impact of a diet supplemented with egg yolks of modified content, having in mind the type of fat added to the laying hens diet, on the brain lipids and their fatty acid composition in rats. During four weeks of the experiment, 64 Wistar rats, divided into four groups of 16 animals each (eight animals of both sexes, were fed the commercial rat feed (group C, or the feed that contained 70% of the commercial rat feed and 30% of freshly boiled yolks from the eggs originating from laying hens fed with 3% fish oil (group F, 3% palm olein (group P or 3% lard (group L. Concentration and content of total lipids and total cholesterol, as well as the fatty-acid composition of the total brain lipids were determined in the lipid extracts of the rats brains. Under unfavourable conditions, which in our case could be high dietary intake of the total fat due to egg yolk addition, the amount of total fat in the brain tissue or the mass of the organ itself can be changed. Applied dietary treatments could also influence the level of de novo synthesis of total cholesterol in the rat brain. High dietary fat intake, as well as the fat quality regarding its fatty acid composition, appear to be able to significantly influence the fatty acid profile of the total brain lipids in adult rats, whereas the level and quality of the changes also depend on sex.

  9. Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain.

    Science.gov (United States)

    Ashafaq, Mohammad; Tabassum, Heena; Vishnoi, Shruti; Salman, Mohd; Raisuddin, Sheikh; Parvez, Suhel

    2016-03-23

    Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat.

  10. Garlic extract attenuates brain mitochondrial dysfunction and cognitive deficit in obese-insulin resistant rats.

    Science.gov (United States)

    Pintana, Hiranya; Sripetchwandee, Jirapas; Supakul, Luerat; Apaijai, Nattayaporn; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-12-01

    Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg(-1)·day(-1)) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.

  11. Irradiation of rat brain reduces P-glycoprotein expression and function

    OpenAIRE

    Bart, J.; Nagengast, W B; Coppes, R P; Wegman, T D; van der Graaf, W T A; Groen, H J M; Vaalburg, W; de Vries, E G E; Hendrikse, N.H.

    2007-01-01

    The blood–brain barrier (BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P-glycoprotein (P-gp), expressed on brain capillary endothelial cells, is part of the BBB. P-gp expression on capillary endothelium decreases 5 days after brain irradiation, which may reduce P-gp function and increase brain levels of P-gp substrates. To elucidate whether radiation therapy reduces P-gp expression and function in the brain, right hemispheres of rats wer...

  12. Generation of primary cultures of bovine brain endothelial cells and setup of cocultures with rat astrocytes

    DEFF Research Database (Denmark)

    Helms, Hans C; Brodin, Birger

    2014-01-01

    In vitro models of the blood-brain barrier are useful tools to study blood-brain barrier function as well as drug permeation from the systemic circulation to the brain parenchyma. However, a large number of the available in vitro models fail to reflect the tightness of the in vivo blood-brain...... barrier. The present protocol describes the setup of an in vitro coculture model based on primary cultures of endothelial cells from bovine brain microvessels and primary cultures of rat astrocytes. The model displays a high electrical tightness and expresses blood-brain barrier marker proteins....

  13. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  14. Beneficial influence of physical exercise following status epilepticus in the immature brain of rats.

    Science.gov (United States)

    Gomes, F G Novaes; Gomes Da Silva, S; Cavalheiro, E A; Arida, R M

    2014-08-22

    Studies in adult animals have demonstrated a beneficial effect of physical exercise on epileptic insults. Although the effects of physical exercise on the mature nervous system are well documented, its influence on the developing nervous system subjected to injuries in childhood has been little explored. The purpose of our study was to investigate whether a physical exercise program applied during brain development could influence the hippocampal plasticity of rats submitted to status epilepticus (SE) induced by pilocarpine model at two different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28 (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX), SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise program, histological and behavioral (water maze) analyses were performed. Our results showed that only animals subjected to pilocarpine-induced SE at P28 presented spontaneous seizures during the observational period. A significant reduction in seizure frequency was observed in the SE/EX group compared to the SE group. In adulthood, animals submitted to early-life SE displayed impairment in long-term memory in the water maze task, while the exercise program reversed this deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and reduced pro-apoptotic response (Bax staining) in animals of both ages of SE induction (P18/28). Exercise also modified the brain-derived neurotrophic factor (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals subjected to SE in the postnatal period a physical exercise program brings about beneficial effects on seizure frequency and hippocampal plasticity in later stages of life.

  15. Pulpal responses to cavity preparation in aged rat molars.

    Science.gov (United States)

    Kawagishi, Eriko; Nakakura-Ohshima, Kuniko; Nomura, Shuichi; Ohshima, Hayato

    2006-10-01

    The dentin-pulp complex is capable of repair after tooth injuries including dental procedures. However, few data are available concerning aged changes in pulpal reactions to such injuries. The present study aimed to clarify the capability of defense in aged pulp by investigating the responses of odontoblasts and cells positive for class II major histocompatibility complex (MHC) to cavity preparation in aged rat molars (300-360 days) and by comparing the results with those in young adult rats (100 days). In untreated control teeth, immunoreactivity for intense heat-shock protein (HSP)-25 and nestin was found in odontoblasts, whereas class-II-MHC-positive cells were densely distributed in the periphery of the pulp. Cavity preparation caused two types of pulpal reactions based on the different extent of damage in the aged rats. In the case of severe damage, destruction of the odontoblast layer was conspicuous at the affected site. By 12 h after cavity preparation, numerous class-II-MHC-positive cells appeared along the pulp-dentin border but subsequently disappeared together with HSP-25-immunopositive cells, and finally newly differentiated odontoblast-like cells took the place of the degenerated odontoblasts and acquired immunoreactivity for HSP-25 and nestin by postoperative day 3. In the case of mild damage, no remarkable changes occurred in odontoblasts after operation, and some survived through the experimental stages. These findings indicate that aged pulp tissue still possesses a defense capacity, and that a variety of reactions can occur depending on the difference in the status of dentinal tubules and/or odontoblast processes in individuals.

  16. Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats.

    Science.gov (United States)

    Mori, M; Wilber, J F; Nakamoto, T

    1984-12-17

    We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.

  17. Daicong solution effects on brain ultrastructure in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Qian Yue; Yuling Ding; Hongyan Wang; Shumei Zhao; Shengming Zhang; Hongjuan Wu; Yiguang Wang; Fengjie Li; Yuanyuan Yang; Juanjuan Liu

    2008-01-01

    BACKGROUND: Infusion of kainic acid into the basal nuclei induces neuronal excitotoxicity, degeneration, and necrosis, resulting in disturbed learning and memory functions.OBJECTIVE: To explore the effects of different doses of traditional Chinese medicine Daicong solution on brain ultrastructure in a rat model of Alzheimer's disease.DESIGN, TIME AND SETTING: The randomized, controlled, cellular morphology experiment was performed at the Shandong Provincial Key Laboratory of Molecular Immunology of Weifang Medical University, China from October 2006 to March 2007.MATERIALS: Fifty healthy, Sprague Dawley rats, aged 22-months, were used to establish rat models of Alzheimer's disease. The Morris water maze was prepared at the Pharmacometrics Key Laboratory of Weifang Medical University in Shandong Province of China. Traditional Chinese medicine Daicong solution (crude drug 1 g/mL), composed of radix ginseng, rehmannia dried rhizome, anemarrhenae and radix astragali, was produced by the Department of Pharmacy of Hospital Affiliated to Weifang Medical University. Kainic acid was provided by Professor Xiuyan Li from Weifang Medical University.METHODS: A total of 40 model rats were equally and randomly divided into four groups: dementia model, low-dose Daicong solution (5 g/kg/d), moderate-dose Daicong solution (10 g/kg/d), and high-dose Daicong solution (20 g/kg/d). An additional 10 healthy rats served as the normal control group. Rats in the dementia model and normal control groups received saline (10 mL/kg/d).MAIN OUTCOME MEASURES: Neural cell ultrastructure was observed utilizing electron microscopy after 1 month of respective treatments.RESULTS: Compared with the normal control group, electron density and the number of ribosomes were significantly reduced in neuronal cytoplasm, and many lipofuscin grains and vacuole-like changes were observed in mitochondria in the dementia model group. In addition, nuclear chromatin presented with different sizes of plaque

  18. Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats.

    Science.gov (United States)

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2014-06-01

    Astrocytes are responsible for modulating neurotransmitter systems and synaptic information processing, ionic homeostasis, energy metabolism, maintenance of the blood-brain barrier, and antioxidant and inflammatory responses. Our group recently published a culture model of cortical astrocytes obtained from adult Wistar rats. In this study, we established an in vitro model for hippocampal astrocyte cultures from adult (90 days old) and aged (180 days old) Wistar rats. Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and neuroprotective effects that modulate glial functions. Here, we evaluated the effects of resveratrol on GSH content, GS activity, TNF-α and IL-1β levels in hippocampal astrocytes from newborn, adult and aged Wistar rats. We observed a decrease in antioxidant defenses and an increase in the inflammatory response in hippocampal astrocytes from adult and aged rats compared to classical astrocyte cultures from newborn rats. Resveratrol prevented these effects. These findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with antioxidant and anti-inflammatory activities.

  19. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats.

    Science.gov (United States)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

    2014-03-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

  20. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  1. Liver mitochondrial dysfunction is reverted by insulin-like growth factor II (IGF-II in aging rats

    Directory of Open Access Journals (Sweden)

    Castilla-Cortazar Inma

    2011-07-01

    Full Text Available Abstract Background Serum IGF-I and IGF-II levels decline with age. IGF-I replacement therapy reduces the impact of age in rats. We have recently reported that IGF-II is able to act, in part, as an analogous of IGF-I in aging rats reducing oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities. Since mitochondria seem to be the most important cellular target of IGF-I, the aim of this work was to investigate whether the cytoprotective actions of IGF-II therapy are mediated by mitochondrial protection. Methods Three groups of rats were included in the experimental protocol young controls (17 weeks old; untreated old rats (103 weeks old; and aging rats (103 weeks old treated with IGF-II (2 μg/100 g body weight and day for 30 days. Results Compared with young controls, untreated old rats showed an increase of oxidative damage in isolated mitochondria with a dysfunction characterized by: reduction of mitochondrial membrane potential (MMP and ATP synthesis and increase of intramitochondrial free radicals production and proton leak rates. In addition, in untreated old rats mitochondrial respiration was not blocked by atractyloside. In accordance, old rats showed an overexpression of the active fragment of caspases 3 and 9 in liver homogenates. IGF-II therapy corrected all of these parameters of mitochondrial dysfunction and reduced activation of caspases. Conclusions The cytoprotective effects of IGF-II are related to mitochondrial protection leading to increased ATP production reducing free radical generation, oxidative damage and apoptosis.

  2. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    Directory of Open Access Journals (Sweden)

    Bruce eCrosson

    2015-05-01

    Full Text Available The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  3. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease.

    Science.gov (United States)

    Crosson, Bruce; McGregor, Keith M; Nocera, Joe R; Drucker, Jonathan H; Tran, Stella M; Butler, Andrew J

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  4. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

    NARCIS (Netherlands)

    Zwiers, M.P.; Buitelaar, J.K.; Fernandez, G.S.E.; Flor, H.; Fouche, J.P.; Frouin, V.; Wolfers, T.; Fisher, S.E.; Francks, C.

    2016-01-01

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymm

  5. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats.

    Science.gov (United States)

    Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo

    2016-05-01

    Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease.

  6. Tumor necrosis factor α antibody prevents brain damage of rats with acute necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Kai-Zong Li; Ke-Feng Dou

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor á (TNFα) antibody on pancreatic encephalopathy in rats.METHODS:One hundred and twenty SD rats were randomly divided into normal control group,acute necrotizing pancreatitis group and TNFα antibody treated group.Acute hemorrhage necrotizing pancreatitis model in rats was induced by retrograde injection of 50 g/L sodium taurocholate into the pancreatobiliary duct.Serum TNFα was detected and animals were killed 12 h after drug administration.Changes in content of brain water,MDA and SOD as well as leucocyte adhesion of brain microvessels were measured.RESULTS:In TNFα antibody treated group,serum TNFálevel was decreased.Content of brain water,MDA and SOD as well as leucocyte adhesion were decreased significantly in comparison with those of acute necrotizing pancreatitis group (P<0.05).CONCLUSION:TNFα antibody can alleviate the brain damage of rats with acute hemorrhage necrotizing pancreatitis.

  7. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  8. BRAIN VOLUMES OF THE LAMB, RAT AND BIRD DO NOT SHOW HEMISPHERIC ASYMMETRY: A STEREOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    Bünyamin Sahin

    2011-05-01

    Full Text Available It is well known that there are functional differences between right and left brain hemispheres. However, it is not clear whether these functional differences are reflected in morphometric differences. This study was carried out to investigate the right-left asymmetry, and sex and species differences of the brains using the Cavalieri principle for volume estimation. Seventeen lambs, 10 rats and 12 avian brains were used to estimate brain volumes. A transparent point grid was superimposed on the slices of lamb brains directly and the slices of the rat and avian brains were projected onto a screen at 10x magnification. Surface areas of the cut slice faces were estimated by simply counting the points that hit the slices. Mean brain volumes were 37.74 cm3, 598.95 mm3 and 730.38 mm3 and the coefficients of variations were 0.08, 0.05 and 0.05 for lamb, rat and avian brains respectively. The differences between left and right hemispheres did not show statistical significance (P > 0.05. However, the male brain volumes were larger than the females for the lamb and bird (P < 0.05. In light of such findings, it will be necessary to evaluate neuron number of the brain hemispheres to provide more useful data regarding inter-hemispheric brain asymmetry.

  9. A high-salt diet further impairs age-associated declines in cognitive, behavioral, and cardiovascular functions in male Fischer brown Norway rats.

    Science.gov (United States)

    Chugh, Gaurav; Asghar, Mohammad; Patki, Gaurav; Bohat, Ritu; Jafri, Faizan; Allam, Farida; Dao, An T; Mowrey, Christopher; Alkadhi, Karim; Salim, Samina

    2013-09-01

    Aging-associated declines in cognitive, emotional, and cardiovascular function are well known. Environmental stress triggers critical changes in the brain, further compromising cardiovascular and behavioral health during aging. Excessive dietary salt intake is one such stressor. Here, we tested the effect of high salt (HS) on anxiety, learning-memory function, and blood pressure (BP) in male Fischer brown Norway (FBN) rats. Adult (A; 2 mo) and old (O; 20 mo) male rats were fed normal-salt (NS; 0.4% NaCl) or HS (8% NaCl) diets for 4 wk after being implanted with telemeter probes for conscious BP measurement. Thereafter, tests to assess anxiety-like behavior and learning-memory were conducted. The rats were then killed, and samples of plasma, urine, and brain tissue were collected. We found that systolic BP was higher in O-NS (117 ± 1.2 mm Hg) than in A-NS (105 ± 0.8 mm Hg) rats (P < 0.05). Furthermore, BP was higher in O-HS (124 ± 1.4 mm Hg) than in O-NS (117 ± 1.2 mm Hg) rats (P < 0.05). Moreover, anxiety-like behavior (light-dark and open-field tests) was not different between A-NS and O-NS rats but was greater in O-HS rats than in A-NS, O-NS, or A-HS rats (P < 0.05). Short-term memory (radial arm water maze test) was similar in A-NS and O-NS rats but was significantly impaired in O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05). Furthermore, oxidative stress variables (in plasma, urine, and brain) as well as corticosterone (plasma) were greater in O-HS rats when compared with A-NS, O-NS, or A-HS rats (P < 0.05). The antioxidant enzyme glyoxalase-1 expression was selectively reduced in the hippocampus and amygdala of O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05), whereas other antioxidant enzymes, glutathione reductase 1, manganese superoxide dismutase (SOD), and Cu/Zn SOD remained unchanged. We suggest that salt-sensitive hypertension and behavioral derangement are associated with a redox imbalance in the brain of aged FBN rats.

  10. [Age-related characteristics of experimental hypothyroidism in rats].

    Science.gov (United States)

    Hromakova, I A; Zil'berman, S Ts; Konovalenko, O O

    2002-01-01

    The rate of both the synthesis of liver and plasma proteins and RNA-1 and RNA-2 polymerase activities in liver were studied in rats of various ages at experimental hypothyroidism. There has been marked more significant decrease in plasma protein synthesis with age. Both the rate of liver and plasma protein synthesis have been shown to be reduced at experimental hypothyroidism but synthesis of plasma proteins was inhibited to a greater extent. Considerable changes were observed neither in liver and plasma protein synthesis nor in the balance between these two groups of the protein synthesis in old rats. RNA-1 and RNA-2 polymerase activities decreased at hypothyroidism. At all ages the activity of bound enzymes decreased to a larger extent as compared to free forms. The activity of RNA-polymerase 2 was more inhibited than that of RNA-polymerase 1. Reducing protein- and RNA-synthetic processes in the liver with age correlated with the peculiarities of the carbohydrate metabolism: in those young animals with an impaired glucose tolerance the inhibitory effect of hypothyroidism on the intensity of protein and RNA synthesis was more potent as compared to old animals.

  11. The expression of TRPA1 mRNA in the rat brain

    Institute of Scientific and Technical Information of China (English)

    Peng Du; Shua Li; Jinyu Zheng; Zhi-yuan Yu; Minjie Xie; Wei Wang

    2006-01-01

    Objective: To investigate the distribution of TRPA1 (one kind of the TRP-like ion channel family) channel in the hippocampus and cerebral cortex of rat. Methods: RT-PCR was used to amplify the fragment of TRPA1 in the DRG (dorsal root ganglion), hippocampus and cerebral cortex of adult SD rat. In situ hybridization staining was used to show the distribution of TRPA1 mRNA in the hippocampus and cerebral cortex of adult rat brain. Results: Both RT-PCR and in situ hybridization staining showed that TRPA1 mRNA was expressed in hippocampus and cerebral cortex of the adult rat brain. Conclusion: Ourresults suggest that there is expression of TRPA1 mRNA both in the hippocampus and cerebral cortex of the adult rat brain.

  12. Nerve protective effect of rhTPO and G-CSF on hypoxic ischemic brain damage in rats

    Institute of Scientific and Technical Information of China (English)

    Hong-Xia Zhou; Chun-Lai Zhang; Yue-Hong Li; Yu-Xin Zhang; Zi-Feng Wei; Xi Wang Meng Ling-Li

    2014-01-01

    Objective:To observe the protection effect of rhTPO and granulocyte colony stimulating factor (G-CSF) on brain nerve after hypoxic ischemic brain damage(HIBD) in neonatal rats, exploring new ways for the laboratory basis of treatment for hypoxic ischemic encephalopathy, and provide for possible.Methods:A total of120 newbornSD rats aging7 d were randomly divided into control group, model group,TPO group andG-CSF group, using the method of blockingleft carotid artery to establishHIBD model.The left carotid artery was only seperated rather than blocked in the control group; after modeling, saline injection, rhTPO treatment andG-CSF treatment were adopted in the model group,TPO group andG-CSF group respectively.Then10 rats of4 groups were executed atDay3,7,14 after modeling, brain tissue was extracted to observe the brain damage;Immunohistochemical method was used to observe the histopathological changes of brain tissue and changes of nest protein(nestin) expression.Results:Injured brain mass of model group,TPO group andG-CSF group were significantly higher than that of control group at corresponding time point(P<0.05).Injured brain mass ofTPO group andG-CSF group were significantly lower than that of model group(P<0.05), and with the increase of age, more significant increasing trend.AtDay3 after modeling, the expression of nestin positive cells in cerebral cortex of model group,TPO group andG-CSF group increased significantly than that of control group(P<0.05); nestin positive cells ofG-CSF group outnumberedTPO group significantly (P<0.05).Conclusions:The earlyTPO,G-CSF treatment ofHIBD rats can improve brain function after hypoxia ischemia by neural protection.G-CSF can promote the differentiation of neural cells proliferation, and reduce degeneration and necrosis of nerve cells.

  13. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    Science.gov (United States)

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  14. Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

    DEFF Research Database (Denmark)

    1990-01-01

    A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... the five NCAM mRNAs in rat brain....

  15. Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Annika [Turku University Hospital, Department of Pediatrics, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Parkkola, Riitta [University of Turku and Turku University Hospital, Department of Radiology and Turku PET Center, PO Box 52, Turku (Finland); Lehtonen, Liisa; Maunu, Jonna; Lapinleimu, Helena [University of Turku and Turku University Hospital, Department of Pediatrics, Turku (Finland); Munck, Petriina [Turku University Hospital, Department of Pediatrics, Turku (Finland); University of Turku, Department of Psychology, Turku (Finland); Haataja, Leena [University of Turku and Turku University Hospital, Department of Pediatric Neurology, Turku (Finland)

    2011-08-15

    Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children. (orig.)

  16. Aging increases upper airway collapsibility in Fischer 344 rats.

    Science.gov (United States)

    Ray, Andrew D; Ogasa, Toshiyuki; Magalang, Ulysses J; Krasney, John A; Farkas, Gaspar A

    2008-11-01

    The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = -7.1 +/- 0.6 (SE) vs. -9.5 +/- 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: -4.2 +/- 0.5 cmH2O; Y: -5.4 +/- 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: -11.3 +/- 1.0 cmH2O; Y: -10.2 +/- 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 +/- 2.5 vs. 21.7 +/- 1.7%; P collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.

  17. Effects of morphine dependence and withdrawal on levels of neurosteroids in rat brain

    Institute of Scientific and Technical Information of China (English)

    Cai-zhen YAN; Yan-ning HOU

    2004-01-01

    AIM: To investigate the effects of morphine dependence and withdrawal on the concentrations of neurosteroids in rat brain. METHODS: A method of simultaneous quantification of neurosteroids by gas chromatography-mass spectrometry (GC-MS) had been established. RESULTS: The chronic morphine administration (ip) resulted in a marked decrease in the brain concentrations of pregnenolone (PREG), progesterone (PROG), and pregenenolone sulfate (PREGS) in rats killed 6 h after the last treatment. In contrast, there were no significant effects of morphine dependence on the brain concentrations of allopregnanolone (AP), dihydroepiandrosterone (DHEA), and dihydroepiandrosterone sulfate (DHEAS). Naloxone-induced withdrawal produced a significant increase in the concentrations of PREG, PROG, AP, DHEA, PREGS, and DHEAS as compared with the control group.CONCLUSION: Morphine dependence and withdrawal affected the concentrations of neurosteroids in rat brain,which suggests that endogenous neurosteroids in brain might be related to the development of morphine dependence and withdrawal.

  18. Increased expression of aquaporin-4 in brain tissue of amygdala-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Yinghui Chen; Yongbo Zhao

    2011-01-01

    Recurrent epileptic seizures can lead to brain edema, indicating that water regulation may be perturbed by seizures.We hypothesized that the expression of the brain water channel aquaporin-4 (AQP-4) may be upregulated in the epileptic brain.In the present study, we established the amygdala kindling model of epilepsy, and quantified AQP-4 protein and mRNA levels, using reverse transcription-PCR, immunohistochemistry and western blotting, in epileptic and control rats.We found that AQP-4 was overexpressed in the cerebral cortex of rats with epilepsy compared with controls.These findings show that AQP-4 is highly expressed in the brain of amygdala-kindled rats, suggesting that repeated seizures affect water homeostasis in the brain.

  19. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  20. Hyperammonemia,brain edema and blood-brain barrier alterations in prehepatic portal hypertensive rats and paravrtamol intoxication

    Institute of Scientific and Technical Information of China (English)

    Camila Scorticati; Juan P. Prestifilippo; Francisco X. Eizayaga; José L. Castro; Salvador Romay; Maria A. Fernández; Abraham Lemberg; Juan C. Perazzo

    2004-01-01

    AIM: To study the blood-brain barrier integrity, brain edema,animal behavior and ammonia plasma levels in prehepatic portal hypertensive rats with and without acute liver intoxication.METHODS: Adults male Wistar rats were divided into four groups. Group Ⅰ: sham operation; Ⅱ: Prehepatic portal hypertension, produced by partial portal vein ligation; Ⅲ:Acetaminophen intoxication and Ⅳ: Prehepatic portal hypertension plus acetaminophen. Acetaminophen was administered to produce acute hepatic injury. Portal pressure, liver serum enzymes and ammonia plasma levels were determined. Brain cortex water content was registered and trypan blue was utilized to study blood brain barrier integrity. Reflexes and behavioral tests were recorded.RESULTS: Portal hypertension was significantly elevated in groups Ⅱ and Ⅳ. Liver enzymes and ammonia plasma levels were increased in groups Ⅱ, Ⅳ and Ⅳ. Prehepatic portal hypertension (group Ⅱ), acetaminophen intoxication (group Ⅲ) and both (group Ⅳ) had changes in the blood brain-barrier integrity (trypan blue) and hyperammonemia. Cortical edema was present in rats with acute hepatic injury in groups Ⅲ and Ⅳ. Behavioral test (rota rod) was altered in group Ⅳ.CONCLUSION: These results suggest the possibility of another pathway for cortical edema production because blood brain barrier was altered (vasogenic) and hyperammonemia was registered (cytotoxic). Group Ⅳ, with behavioral altered test, can be considered as a model for study at an early stage of portal-systemic encephalopathy.

  1. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.

    Science.gov (United States)

    Kochkina, Ekaterina G; Plesneva, Svetlana A; Vasilev, Dmitrii S; Zhuravin, Igor A; Turner, Anthony J; Nalivaeva, Natalia N

    2015-08-01

    Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ). In the normally functioning brain Aβ catabolism is regulated by a cohort of proteolytic enzymes including insulin-degrading enzyme (IDE) and their deficit with ageing can result in Aβ accumulation and increased risk of AD. The aim of this study was a comparative analysis of IDE expression in the brain structures involved in AD, as well as in peripheral organs (the liver and kidney) of rats, during natural ageing and after experimentally-induced diabetes. It was found that ageing is accompanied by a significant decrease of IDE mRNA and protein content in the liver (by 32 and 81%) and brain structures (in the cortex by 58 and 47% and in the striatum by 53 and 68%, respectively). In diabetic animals, IDE protein level was increased in the liver (by 36%) and in the striatum (by 42%) while in the brain cortex and hippocampus it was 20-30% lower than in control animals. No significant IDE protein changes were observed in the kidney of diabetic rats. These data testify that ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Aβ was reported in AD patients, which might be one of the factors predisposing to development of the sporadic form of AD in the elderly, and especially in diabetics.

  2. Improving effects of long-term growth hormone treatment on monoaminergic neurotransmission and related behavioral tests in aged rats.

    Science.gov (United States)

    Esteban, Susana; Garau, Celia; Aparicio, Sara; Moranta, David; Barceló, Pere; Ramis, Margarita; Tresguerres, Jesús A F; Rial, Rubén

    2010-12-01

    An age-related decline in cognitive functions and physical performance has been associated with reductions in growth hormone (GH) secretion and brain neurotransmitter function. In vivo experiments were performed to study the long-term effects of exogenously administered GH on the central monoaminergic neurotransmitters serotonin, dopamine, and noradrenaline and behavioral tests in old Wistar rats. The accumulation of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in vivo. Also, the content of the neurotransmitters serotonin, dopamine, and noradrenaline and some metabolites was measured by high-pressure liquid chromatography (HPLC) in the hippocampus and striatum, brain regions involved in adult memory processing and motor coordination. The age-related decline observed in all the neurochemical parameters in control rats was significantly reversed after repeated subcutaneous administration of GH (2 mg/kg per day, 4 weeks). Thus, GH treatment exerted a long-term effect on serotonin, dopamine, and noradrenaline neurotransmission by enhancing neurotransmitter synthesis and metabolism in aged rats. The results obtained after examining working memory tasks in the eight-radial maze and motor ability in the Rotarod treadmill in aged rats were consistent with these neurochemical data; both tests were significantly improved after chronic GH treatment. Overall, these in vivo findings suggest that the positive effects induced by GH on serotonin, dopamine, and noradrenaline neurotransmitters might explain, at least in part, the effects of chronic GH treatment in improving cognitive and motor ability in aged rats, and could aid in preventing or delaying deficits in monoamines associated with learning or motor disabilities.

  3. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    Science.gov (United States)

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  4. Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

    Science.gov (United States)

    Abreu, Renata Viana; Silva-Oliveira, Eliane Moretto; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Moraes-Santos, Tasso

    2011-10-01

    Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive

  5. Effect of L-arginine on metabolism of polyamines in rat's brain with extrahepatic cholestasis.

    Science.gov (United States)

    Sokolovic, Dusan; Bjelakovic, Gordana; Nikolic, Jelenka; Djindjic, Boris; Pavlovic, Dusica; Kocic, Gordana; Stojanovic, Ivana; Pavlovic, Voja

    2010-01-01

    Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of L-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with L-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with L-arginine. Increased plasma gamma-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of L-arginine (P < 0.001). Cholestasis increased the brain's putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of L-arginine in BDL rats prevents metabolic disorders of polyamines and establishes a neuroprotective role in the brain during cholestasis.

  6. Effects of tetrahydroxystilbene - glucoside on Animal Models of Dementia or Brain Aging

    Institute of Scientific and Technical Information of China (English)

    LinLi; JinChu; LiLiu; LingZhao; LanZhang

    2004-01-01

    Aim: To investigate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside(TSG) from a Chinese Medicinal Herb polygonum multiflorum on dementia or brain aging. Methods. The brain aging model of mice was developed by s. c. injection of D-galactose (50mg/kg/day) for 60 days. The Alzheimer disease (AD) model of mice

  7. Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

    Science.gov (United States)

    Veraart, Jelle; Leergaard, Trygve B; Antonsen, Bjørnar T; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G Allan; Verhoye, Marleen; Sijbers, Jan

    2011-10-15

    Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

  8. Aerobic exercise regulates Rho/cofilin pathways to rescue synaptic loss in aged rats

    Science.gov (United States)

    Li, Yan; Zhao, Li; Gu, Boya; Cai, Jiajia; Lv, Yuanyuan; Yu, Laikang

    2017-01-01

    Purpose The role of exercise to prevent or reverse aging-induced cognitive decline has been widely reported. This neuroprotection is associated with changes in the synaptic structure plasticity. However, the mechanisms of exercise-induced synaptic plasticity in the aging brain are still unclear. Thus, the aim of the present study is to investigate the aging-related alterations of Rho-GTPase and the modulatory influences of exercise training. Methods Young and old rats were used in this study. Old rats were subjected to different schedules of aerobic exercise (12 m/min, 60 min/d, 3d/w or 5d/w) or kept sedentary for 12 w. After 12 w of aerobic exercise, the synapse density in the cortex and hippocampus was detected with immunofluorescent staining using synaptophysin as a marker. The total protein levels of RhoA, Rac1, Cdc42 and cofilin in the cortex and hippocampus were detected with Western Blot. The activities of RhoA, Rac1 and Cdc42 were determined using a pull down assay. Results We found that synapse loss occurred in aging rats. However, the change of expression and activity of RhoA, Rac1 and Cdc42 was different in the cortex and hippocampus. In the cortex, the expression and activity of Rac1 and Cdc42 was greatly increased with aging, whereas there were no changes in the expression and activity of RhoA. In the hippocampus, the expression and activity of Rac1 and Cdc42 was greatly decreased and there were no changes in the expression and activity of RhoA. As a major downstream substrate of the Rho GTPase family, the increased expression of cofilin was only observed in the cortex. High frequency exercise ameliorated all aging-related changes in the cortex and hippocampus. Conclusions These data suggest that aerobic exercise reverses synapse loss in the cortex and hippocampus in aging rats, which might be related to the regulation of Rho GTPases. PMID:28152068

  9. Immunocytochemical study on the intracellular localization of the type 2 glucocorticoid receptor in the rat brain

    NARCIS (Netherlands)

    Eekelen, J.A.M. van; Kiss, J.Z.; Westphal, H.M.; Kloet, E.R. de

    1987-01-01

    The localization of the glucocorticoid receptor (GR) (type 2) in the rat brain was studied with immunocytochemistry using a monoclonal antibody against the rat liver GR. Strong GR immunoreactivity (GR-ir) was observed in neurons of limbic and brainstem structures known to be associated with the stre

  10. Expression of annexin and Annexin-mRNA in rat brain under influence of steroid drugs

    NARCIS (Netherlands)

    Voermans, PH; Go, KG; ter Horst, GJ; Ruiters, MHJ; Solito, E; Parente, L; James, HE; Marshall, LF; Reulen, HJ; Baethmann, A; Marmarou, A; Ito, U; Hoff, JT; Kuroiwa, T; Czernicki, Z

    1997-01-01

    Brain tissue of rats pretreated with methylprednisolone or with the 21-aminosteroid U74389F, and that of untreated control rats, was assessed for the expression of Annexin-l (Anx-1) and the transcription of its mRNA. For this purpose Anx-1 cDNA was amplified and simultaneously a T7-RNA-polymerase pr

  11. Comparative proteomics of rat brain in the BCNU-induced model of cortical dysplasia

    Institute of Scientific and Technical Information of China (English)

    郭谊

    2014-01-01

    Objective To screen the differential proteins in the brain(neocortex and hippocampus)between the rats with cortical dysplasia(CD)and control ones,and investigate the role of their alteration in the development of epilepsy in CD.Methods Cortical dysplasia was induced in rat pups via in utero delivery of BCNU.A two-dimensional electrophoresis

  12. The effects of trypsin on rat brain astrocyte activation.

    Directory of Open Access Journals (Sweden)

    Masoud Fereidoni

    2013-12-01

    Full Text Available Astrocytes are cells within the central nervous system which are activated in a wide spectrum of infections, and autoimmune and neurodegenerative diseases. In pathologic states, they produce inflammatory cytokines, chemokines, and nitric oxide (NO, and sometimes they induce apoptosis. Their protease-activated receptors (PARs can be activated by proteases, e.g. thrombin and trypsin, which are important in brain inflammation. The current study aimed to investigate the effects of different concentrations of trypsin (1 to 100U/ml on cultured astrocytes.In the present study, two-day rat infants' brains were isolated and homogenized after meninges removal, then cultivated in DMEM + 10% FBS medium. 10 days later, astrocytes were harvested and recultivated for more purification (up to 95%, using Immunocytochemistry method, in order to be employed for tests. They were affected by different concentrations of trypsin (1, 5, 10, 15, 20, 40, 60, 80, and 100 U/ml. To reveal the inflammation progress, NO concentrations (the Griess test were assessed after 24 and 48 hours.The results showed that trypsin concentration up to 20 U/ml caused a significant increase in NO, in a dose-dependent manner, on cultured astrocytes (P < 0.001. Trypsin 20 U/ml increased NO production fivefold the control group (P < 0.001. At higher concentrations than 20 U/ml, NO production diminished (P < 0.001. At 100 U/ml, NO production was less than the control group (P < 0.001.Inflammatory effects of trypsin 5-20 U/ml are probably due to the stimulation of astrocytes' PAR-2 receptors and the increasing of the activation of NF-κB, PKC, MAPKs. Stimulation of astrocytes' PAR-2 receptors causes an increase in iNOS activation which in turn leads to NO production. However, higher trypsin concentration possibly made astrocyte apoptosis; therefore, NO production diminished. These assumptions need to be further investigated.

  13. The metabolism of malate by cultured rat brain astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, M.C.; Tildon, J.T.; Couto, R.; Stevenson, J.H.; Caprio, F.J. (Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA))

    1990-12-01

    Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

  14. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

    Science.gov (United States)

    Servatius, Richard J; Marx, Christine E; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D; Naylor, Jennifer C; Pang, Kevin C H

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  15. Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Richard J Servatius

    2016-08-01

    Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  16. Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats.   Methods: The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay.   Results: The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury.   Conclusions: It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

  17. Serial Post-mortem Relaxometry in the Normal Rat Brain and Following Stroke

    OpenAIRE

    Fagan, Andrew J.; Mullin, JM; Gallagher, L; Hadley, DM; Macrae, IM; Condon, B

    2008-01-01

    PUBLISHED Purpose: Investigation of MRI for non-invasive autopsy via measurements of serial changes in relaxation parameters of the rat brain during the post-mortem interval. Materials and Methods: Post-mortem relaxometry measurements were performed before and hourly after death for 24 hours on five control rats and five rats which underwent middle cerebral artery occlusion. Analyses were performed on representative regions of grey, white, and mixed grey/white matter structures. ...

  18. Brain Na+, K+-ATPase Activity In Aging and Disease

    Science.gov (United States)

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  19. [(11)C]-DASB microPET imaging in the aged rat: frontal and meso-thalamic increases in serotonin transporter binding.

    Science.gov (United States)

    Hoekzema, Elseline; Rojas, Santiago; Herance, Raúl; Pareto, Deborah; Abad, Sergio; Jiménez, Xavier; Figueiras, Francisca P; Popota, Foteini; Ruiz, Alba; Flotats, Núria; Fernández, Francisco J; Rocha, Milagros; Rovira, Mariana; Víctor, Víctor M; Gispert, Juan D

    2011-12-01

    Whereas molecular imaging studies in the aging human brain have predominantly demonstrated reductions in serotonin transporter (5-HTT) availability, the majority of the rodent studies, using autoradiographic methods, report increases in neural 5-HTT levels with age. To our knowledge, however, no previous rodent studies have assessed this topic in vivo, and therefore it remains unclear whether this discrepancy arises from methodological or inter-species differences. We performed an [(11)C]-DASB microPET study to evaluate the effects of aging on 5-HTT availability in the rat brain. To generate binding potential estimates, quantitative tracer kinetic modeling was applied using the simplified reference tissue model. A global increase in whole-brain [(11)C]-DASB binding potential was observed in the aged rats in comparison to the control group. More specifically, regional analyses revealed a highly significant increase in 5-HTT binding in the medial frontal cortex, and more modest increments in the midbrain/thalamus. Our results suggest that the frontal cortex represents a site of robust age-related alterations in the rat serotonergic system, and stress the need for further research assessing this topic in the human frontal cortex. Moreover, these findings suggest that the reported discrepancies between rodent and human data may reflect a divergence in the aging processes affecting human and rat serotonergic terminals.

  20. Effects of vitamin B-6 nutrition on benzodiazepine (BDZ) receptor binding in the developing rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Borek, J.P.; Guilarte, T.R. (Johns Hopkins Univ., Baltimore, MD (United States))

    1990-02-26

    A dietary deficiency of vitamin B-6 promotes seizure activity in neonatal animals and human infants. Previous studied have shown that neonatal vitamin B-6 deprivation results in reduced levels of brain gamma-aminobutyric acid (GABA) and increased binding at the GABA site of the GABA/BDZ receptor complex. Since the GABA and BDZ receptors are allosterically linked, this study was undertaken to determine if vitamin B-6 deprivation had an effect on BDZ receptor binding. Benzodiazepine receptor binding isotherms using {sup 3}H-flunitrazepam as ligand were performed in the presence and absence of 10 {mu}M GABA. The results indicate a significant increase in the binding affinity (Kd) in the presence of GABA in cerebellar membranes from deficient rat pups at 14 days of age with no effect on receptor number (Bmax). By 28 days of age, the increase in Kd was no longer present. No change in Kd or Bmax was observed in cortical tissue from deficient animals at 14 or 28 days of age. Preliminary studies of GABA-enhancement of {sup 3}H-flunitrazepam binding indicate that vitamin B-6 deficiency also induces alterations in the ability of GABA to enhance BZD receptor binding. In summary, these results indicate that the effects of vitamin B-6 deprivation on BDZ receptor binding are region specific and age related.

  1. Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Israel Pérez-Torres

    2016-10-01

    Full Text Available The antioxidant properties of aged garlic extract (AGE on cardiovascular functioning (CF in metabolic syndrome (MS remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS, MS rats (30% sucrose in drinking water from weaning plus saline solution (MS + SS, control rats receiving AGE (C + AGE 125 mg/Kg/12 h and MS rats with AGE (MS + AGE were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01. Cholesterol was decreased by AGE (p = 0.05. Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05. Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001. Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation and AGE improved it (p = 0.001. Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001. Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01. In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.

  2. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    DEFF Research Database (Denmark)

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle

    2013-01-01

    findings to human pathophysiology. This study compares expression of aquaporin-4 in hydrocephalic human brain with human controls and hydrocephalic rat brain. Methods:  Cortical biopsies from patients with chronic hydrocephalus (n=29) were sampled secondary to planned surgical intervention. Aquaporin-4...

  3. Alteration of water-soluble S-100 protein content in microembolized rat brain.

    Directory of Open Access Journals (Sweden)

    Harada,Yasuhiro

    1982-12-01

    Full Text Available The amount of S-100 protein in rat brain embolized with carbon microspheres decreased in parallel with the development of cerebral edema as judged by water content, recovering to the normal range by 24h after embolization. These results suggest the participation of S-100 protein in the permeability characterisitics of nervous system capillaries known as the blood-brain barrier.

  4. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    Science.gov (United States)

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  5. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    Science.gov (United States)

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  6. Localization of Brain Natriuretic Peptide Immunoreactivity in Rat Spinal Cord

    Directory of Open Access Journals (Sweden)

    Essam M Abdelalim

    2016-12-01

    Full Text Available Brain natriuretic peptide (BNP exerts its functions through natriuretic peptide receptors. Recently, BNP has been shown to be involved in a wide range of functions. Previous studies reported BNP expression in the sensory afferent fibers in the dorsal horn of the spinal cord. However, BNP expression and function in the neurons of the central nervous system are still controversial. Therefore, in this study, we investigated BNP expression in the rat spinal cord in detail using RT-PCR and immunohistochemistry. RT-PCR analysis showed that BNP mRNA was present in the spinal cord and DRG. BNP immunoreactivity was observed in different structures of the spinal cord, including the neuronal cell bodies and neuronal processes. BNP immunoreactivity was observed in the dorsal horn of the spinal cord and in the neurons of the intermediate column and ventral horn. Double-immunolabeling showed a high level of BNP expression in the afferent fibers (laminae I-II labeled with calcitonin gene-related peptide (CGRP, suggesting BNP involvement in sensory function. In addition, BNP was co-localized with CGRP and choline acetyltransferase in the motor neurons of the ventral horn. Together, these results indicate that BNP is expressed in sensory and motor systems of the spinal cord, suggesting its involvement in several biological actions on sensory and motor neurons via its binding to NPR-A and/or NPR-B in the DRG and spinal cord.

  7. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  8. Simultaneous MRI and PET imaging of a rat brain

    Science.gov (United States)

    Raylman, Raymond R.; Majewski, Stan; Lemieux, Susan K.; Sendhil Velan, S.; Kross, Brian; Popov, Vladimir; Smith, Mark F.; Weisenberger, Andrew G.; Zorn, Carl; Marano, Gary D.

    2006-12-01

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  9. Simultaneous MRI and PET imaging of a rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Raylman, Raymond R [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Majewski, Stan [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Lemieux, Susan K [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Velan, S Sendhil [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States); Kross, Brian [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Popov, Vladimir [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Smith, Mark F [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Weisenberger, Andrew G [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Zorn, Carl [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Ave., Newport News, VA (United States); Marano, Gary D [Center for Advanced Imaging, Department of Radiology, Box 9236, West Virginia University, Morgantown, WV (United States)

    2006-12-21

    Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

  10. Variance in brain volume with advancing age: implications for defining the limits of normality.

    Directory of Open Access Journals (Sweden)

    David Alexander Dickie

    Full Text Available Statistical models of normal ageing brain tissue volumes may support earlier diagnosis of increasingly common, yet still fatal, neurodegenerative diseases. For example, the statistically defined distribution of normal ageing brain tissue volumes may be used as a reference to assess patient volumes. To date, such models were often derived from mean values which were assumed to represent the distributions and boundaries, i.e. percentile ranks, of brain tissue volume. Since it was previously unknown, the objective of the present study was to determine if this assumption was robust, i.e. whether regression models derived from mean values accurately represented the distributions and boundaries of brain tissue volume at older ages.We acquired T1-w magnetic resonance (MR brain images of 227 normal and 219 Alzheimer's disease (AD subjects (aged 55-89 years from publicly available databanks. Using nonlinear regression within both samples, we compared mean and percentile rank estimates of whole brain tissue volume by age.In both the normal and AD sample, mean regression estimates of brain tissue volume often did not accurately represent percentile rank estimates (errors=-74% to 75%. In the normal sample, mean estimates generally underestimated differences in brain volume at percentile ranks below the mean. Conversely, in the AD sample, mean estimates generally underestimated differences in brain volume at percentile ranks above the mean. Differences between ages at the 5(th percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects.While more data are required to make true population inferences, our results indicate that mean regression estimates may not accurately represent the distributions of ageing brain tissue volumes. This suggests that percentile rank estimates will be required to robustly define the limits of brain tissue volume in normal ageing and neurodegenerative disease.

  11. Amphetamine administration improves neurochemical outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dhillon, H S; Dose, J M; Prasad, R M

    1998-09-07

    This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.

  12. Phospholipase A_2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Multiple systemorgan failure is often compli-cated with SAP and PLA2could play an i mportantrole in the study of brain damages.Through thestudy of makingthe rat SAP model inthis study,thesignificance of PLA2on brain damages was surveyedand reported.Materials and methods1 The rat SAP model and its classificationEighty male Sprague-Dawley rats,weight(300±30)g,were randomly divided into4groups:thecontrol group,the sham-operation group,the SAPgroup and the treat ment group of SAP.The ratswere not given food but...

  13. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats

    OpenAIRE

    R A Kireev; Vara, E. (E.); Tresguerres, J. A. F.

    2013-01-01

    It has been suggested that the age-related decrease in the number of neurons in the hippocampus that leads to alterations in brain function, may be associated with an increase in apoptosis due to the reduced secretion of growth hormone (GH) and/or melatonin in old animals. In order to investigate this possibility, male Wistar rats of 22 months of age were divided into three groups. One group remained untreated and acted as the control group. The second was treated with growth hormone (hGH) fo...

  14. Diet, age, and prior injury status differentially alter behavioral outcomes following concussion in rats.

    Science.gov (United States)

    Mychasiuk, Richelle; Hehar, Harleen; van Waes, Linda; Esser, Michael J

    2015-01-01

    Mild traumatic brain injury (mTBI) or concussion affects a large portion of the population and although many of these individuals recover completely, a small subset of people experience lingering symptomology and poor outcomes. Little is known about the factors that affect individual susceptibility or resilience to poor outcomes after mTBI and there are currently no biomarkers to delineate mTBI diagnosis or prognosis. Based upon the growing literature associated with caloric intake and altered neurological aging and the ambiguous link between repetitive mTBI and progressive neurodegeneration, the current study was designed to examine the effect of a high fat diet (HFD), developmental age, and repetitive mTBI on behavioral outcomes following a mTBI. In addition, telomere length was examined before and after experimental mTBI. Sprague Dawley rats were maintained on a HFD or standard rat chow throughout life (including the prenatal period) and then experienced an mTBI/concussion at P30, P30 and P60, or only at P60. Behavioral outcomes were examined using a test battery that was administered between P61-P80 and included; beam-walking, open field, elevated plus maze, novel context mismatch, Morris water task, and forced swim task. Animals with a P30 mTBI often demonstrated lingering symptomology that was still present during testing at P80. Injuries at P30 and P60 rarely produced cumulative effects, and in some tests (i.e., beam walking), the first injury may have protected the brain from the second injury. Exposure to the high fat diet exacerbated many of the behavioral deficits associated with concussion. Finally, telomere length was shortened following mTBI and was influenced by the animal's dietary intake. Diet, age at the time of injury, and the number of prior concussion incidents differentially contribute to behavioral deficits and may help explain individual variations in susceptibility and resilience to poor outcomes following an mTBI.

  15. The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

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    S. Pejic

    2003-05-01

    Full Text Available The sensitivity of copper,zinc (CuZn- and manganese (Mn-superoxide dismutase (SOD to exogenous estradiol benzoate (EB was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 µg EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%, 8 (72.7% and 15 (81.7%. In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6% disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively. EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8% changed to an inhibitory effect on day 8 (38.4% and disappeared by day 45 when inhibition was detected again (48.7%. In males, the inhibitory effect on this enzyme was observed on days 0 (45.0% and 15 (28.9%, and then disappeared until day 60 when a stimulatory effect was observed (38.4%. EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process.

  16. Hyperbaric oxygen preconditioning attenuates postoperative cognitive impairment in aged rats.

    Science.gov (United States)

    Sun, Li; Xie, Keliang; Zhang, Changsheng; Song, Rui; Zhang, Hong

    2014-06-18

    Cognitive decline after surgery in the elderly population is a major clinical problem with high morbidity. Hyperbaric oxygen (HBO) preconditioning can induce significant neuroprotection against acute neurological injury. We hypothesized that HBO preconditioning would prevent the development of postoperative cognitive impairment. Elderly male rats (20 months old) underwent stabilized tibial fracture operation under general anesthesia after HBO preconditioning (once a day for 5 days). Separate cohorts of animals were tested for cognitive function with fear conditioning and Y-maze tests, or euthanized at different times to assess the blood-brain barrier integrity, systemic and hippocampal proinflammatory cytokines, and caspase-3 activity. Animals exhibited significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after surgery, which were significantly prevented by HBO preconditioning. Furthermore, HBO preconditioning significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1 β (IL-1β), IL-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, HBO preconditioning markedly improved blood-brain barrier integrity and caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that HBO preconditioning could significantly mitigate surgery-induced cognitive impairment, which is strongly associated with the reduction of systemic and hippocampal proinflammatory cytokines and caspase-3 activity.

  17. CT ASSESSMENT OF BRAIN VENTRICULAR SIZE BASED ON AGE AND SEX: A STUDY OF 112 CASES

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    Vinoo

    2013-12-01

    Full Text Available CT being the primary modality of choice in many centers for the diagnosis of brain pathology, normal brain ventricular size measurem ents is an important parameter for the diagnosis of conditions like hydrocephalus, age related atrophic changes and also other brain pathologies producing ventriculomegaly. It is also important for knowing the normal upper and lower limits of the brain ven tricular system in the different age groups, and in both sexes so as to diagnose brain pathology.The ventricular system of the brain undergoes changes with aging and varies with gender.Our study consists of 48 female, and 64 male patients. Apart from the v entricular measurements, two ratios and two indices were also calculated – which included the right and left Evan’s ratio, CM index, and ventricular size inde

  18. A common brain network links development, aging, and vulnerability to disease.

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    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  19. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

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    Nutchareeporn Nillert

    2017-01-01

    Full Text Available Neuroinflammation is pathological evidence of Alzheimer’s disease (AD that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β and tumor necrosis factor-α (TNFα, which may lead to neuronal damage and eventual death. Aged garlic extract (AGE has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight, orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42 into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats.

  20. Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats

    Science.gov (United States)

    Nillert, Nutchareeporn; Pannangrong, Wanassanun; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

    2017-01-01

    Neuroinflammation is pathological evidence of Alzheimer’s disease (AD) that likely starts as a host defense response to the damaging effects of the β-amyloid (Aβ) deposits in the brain. The activation of microglia may promote the neurodegenerative process through the release of proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), which may lead to neuronal damage and eventual death. Aged garlic extract (AGE) has been reported to have multiple biological activities, including anti-inflammatory effects. Therefore, the objective of this study was to investigate the effect of AGE on Aβ (1-42)-induced cognitive dysfunction and neuroinflammation. Adult male Wistar rats were given AGE (125, 250, and 500 mg/kg BW, body weight), orally administered, daily for 56 days. They were then injected with 1 μL of aggregated Aβ (1-42) into the lateral ventricles; bilaterally. Seven days later, their recognition memory was evaluated using a novel object recognition (NOR) test. Then the rats were sacrificed to investigate the alteration of microglia cells, IL-1β and TNFα in the cerebral cortex and hippocampus. The results indicated that AGE at doses of 250 and 500 mg/kg BW significantly improved short-term recognition memory in cognitively impaired rats. In addition, AGE significantly minimized the inflammatory response by reducing the activation of microglia and IL-1β to the levels found in the control, which is similar to the results found in Celebrex-treated rats. In conclusion, AGE may be useful for improving the short-term recognition memory and relieve the neuroinflammation in Aβ-induced rats. PMID:28054940

  1. Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain

    LENUS (Irish Health Repository)

    Lyons, Anthony

    2011-03-31

    Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ). IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFNγ-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK) cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2) by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  2. Atorvastatin prevents age-related and amyloid-β-induced microglial activation by blocking interferon-γ release from natural killer cells in the brain

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    Clarke Rachael

    2011-03-01

    Full Text Available Abstract Background Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-γ (IFNγ. IFNγ has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified. Methods Male Wistar rats were used to assess the effect of age and amyloid-β (Aβ on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFNγ, IL-2, monocyte chemoattractant protein-1 (MCP-1 and IFNγ-induced protein 10 kDa (IP-10, expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot. Results Natural killer (NK cells are a major source of IFNγ in the periphery and here we report the presence of CD161+ NKp30+ cells and expression of CD161 and NKp46 in the brain of aged and Aβ-treated rats. Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 (IL-2 by releasing IFNγ. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and Aβ-treated rats. This was paralleled by a decrease in IFNγ, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells. Conclusions We propose that NK cells contribute to the age-related and Aβ-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.

  3. Effect of domoic acid on metabolism of 5-hydroxytryptamine in rat brain.

    Science.gov (United States)

    Arias, B; Arufe, M; Alfonso, M; Duran, R

    1995-04-01

    Domoic acid (Dom) is a neurotoxic secondary amino acid that interacts with the glutamate receptors, producing neurological problems. In the present work, we study the effects of Dom on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete rat brain regions. The effects of Dom on the brain metabolism of serotonin are also discussed in this paper. Dom stimulates the rat brain serotoninergic system, increasing differentially the synthesis and the catabolism of 5-HT and the elimination of 5-HIAA.

  4. [Study on effect of astragali radix polysaccharides in improving learning and memory functions in aged rats and its mechanism].

    Science.gov (United States)

    Yao, Hui; Gu, Li-Jia; Guo, Jian-You

    2014-06-01

    To observe the effect of Astragali Radix polysaccharides (APS) on the learning and memory functions of aged rats, in order to explore its mechanism for improving the learning and memory functions. Natural aging female SD rats were selected in the animal model and randomly divided into the control group, the APS low-dose group (50 mg x kg(-1)), the APS high-dose group (150 mg x kg(-1)) and the piracetam-treated group (560 mg x kg(-1)). They were orally administered with the corresponding drugs for consecutively 60 days. Besides, a young control group was set. The learning and memory functions of the rats were tested by the open-field test and the Morris water maze task. The Western-blot method was used to observe the levels of relevant neural plasticity protein N-methyl-D-aspartate receptor (NMDA receptor) in hippocampus, calcium/calmodulin dependent protein kinase II (CaMK II), protein kinase (PKA), the phosphorylation level of CAMP response element binding protein (CREB) and the protein expression of brain derived neurotrophic factor(BDNF). In this study, the authors found that the learning and memory functions and the hippocampus neural plasticity protein expression of the aged rat group were much lower than that of the young control group (P memory functions of aged rats and the up-regulation in the hippocampus neural plasticity protein expression. The results showed that APS may improve the learning and memory functions of aged rats by increasing the expressions of relevant neural plasticity proteins.

  5. Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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    Martin R.

    2015-08-01

    Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the