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Old Rats (old + rat)

Distribution by Scientific Domains

Life Sciences	59%
Medical Sciences	40%

Distribution within Life Sciences

Neuroscience	18%
Anatomy & Physiology	11%

Selected Abstracts

Aging-Related Increase to Inducible Atrial Fibrillation in the Rat Model

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002
HIDEKI HAYASHI M.D.
Aging and Atrial Fibrillation.Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. Methods and Results: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2,3 months) and 12 old (22,24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 ,M were studied in both groups. Heptanol 2 to 5 ,M promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 ,M, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 ,M. In the old rats, AF could still be induced during perfusion of 2 ,M heptanol. However, when its concentration was raised to 5 and 10 ,M, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. Conclusion: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model. [source]

Free radical generation and oxidative stress with ageing and exercise: Differential effects in the myocardium and liver

ACTA PHYSIOLOGICA, Issue 4 2000
Bejma
Reactive oxygen species and other oxidants are implicated in the mechanisms of biological ageing and exercise-induced tissue damage. The present study examined the effects of ageing and an acute bout of exercise on intracellular oxidant generation, lipid peroxidation, protein oxidation and glutathione (GSH) status in the heart and liver of young adult (8 month, N=24) and old (24 month, N=24) male Fischer 344 rats. Young rats ran on treadmill at 25 m min,1, 5% grade until exhaustion (55.4 ± 2.7 min), whereas old rats ran at 15 m min,1, 5% until exhaustion (58.0 ± 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of intracellular oxidant production, was significantly higher in the homogenates of aged heart and liver compared with their young counterparts. In the isolated heart and liver mitochondria, ageing increased oxidant production by 29 and 32% (P < 0.05), respectively. Acute exercise increased oxidant production in the aged heart but not in the liver. When nicodinamide dinucleotide phosphate (reduced), adenosine diphosphate and Fe3+ were included in the assay, DCFH oxidation rate was 47 and 34% higher (P < 0.05) in the aged heart and liver homogenates, respectively, than the young ones. The age differences in the induced state reached 83 and 140% (P < 0.01) in isolated heart and liver mitochondria, respectively. Lipid peroxidation was increased in the aged liver and exercised aged heart, whereas protein carbonyl content was elevated only in the aged heart (P < 0.05). Although our data using DCFH method probably underestimated cellular oxidant production because of time delay and antioxidant competition, it is clear that oxidative stress was enhanced in both heart and liver with old age. Furthermore, aged myocardium showed greater susceptibility to oxidative stress after heavy exercise. [source]

Influx of calcium through L-type calcium channels in early postnatal regulation of chloride transporters in the rat hippocampus

DEVELOPMENTAL NEUROBIOLOGY, Issue 13 2009
Jennifer G. Bray
Abstract During the early postnatal period, GABAB receptor activation facilitates L-type calcium current in rat hippocampus. One developmental process that L-type current may regulate is the change in expression of the K+Cl, co-transporter (KCC2) and N+K+2Cl, co-transporter (NKCC1), which are involved in the maturation of the GABAergic system. The present study investigated the connection between L-type current, GABAB receptors, and expression of chloride transporters during development. The facilitation of L-type current by GABAB receptors is more prominent in the second week of development, with the highest percentage of cells exhibiting facilitation in cultures isolated from 7 day old rats (37.5%). The protein levels of KCC2 and NKCC1 were investigated to determine the developmental timecourse of expression as well as expression following treatment with an L-type channel antagonist and a GABAB receptor agonist. The time course of both chloride transporters in culture mimics that seen in hippocampal tissue isolated from various ages. KCC2 levels increased drastically in the first two postnatal weeks while NKCC1 remained relatively stable, suggesting that the ratio of the chloride transporters is important in mediating the developmental change in chloride reversal potential. Treatment of cultures with the L-type antagonist nimodipine did not affect protein levels of NKCC1, but significantly decreased the upregulation of KCC2 during the first postnatal week. In addition, calcium current facilitation occurs slightly before the large increase in KCC2 expression. These results suggest that the expression of KCC2 is regulated by calcium influx through L-type channels in the early postnatal period in hippocampal neurons. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]

Detection of carbonyl-modified proteins in interfibrillar rat mitochondria using N, -aminooxymethylcarbonylhydrazino- D -biotin as an aldehyde/keto-reactive probe in combination with Western blot analysis and tandem mass spectrometry

ELECTROPHORESIS, Issue 6 2008
Woon-Gye Chung
Abstract There is now a large body of supporting data available that links oxidative modifications of proteins to a large number of diseases, degenerative disorders and aging. However, the detailed analysis of oxidative protein modifications remains challenging. Here, we report a new efficient method for identification of oxidatively modified proteins in complex biological samples which is based on the use of an aldehyde-reactive probe, N,-aminooxymethylcarbonylhydrazino- D -biotin (ARP), in combination with Western-type analyses and MS. The biotinylated hydroxylamine derivative forms a chemically stable oxime derivative with the aldehyde/keto group found in carbonyl-modified proteins. The biotin tag is detected by avidin affinity staining. ARP-positive proteins are subsequently subjected to in-gel trypsinization and MS/MS for protein identification. We demonstrate the usefulness of the method for the analysis of protein extracts obtained from interfibrillar heart mitochondria (IFM) from young and old rats. In this study, we identified as putative major protein targets of oxidative modifications the mitochondrial matrix protein, aconitase, the inner mitochondrial membrane protein, ADP/ATP translocase, and constituents of the electron transport chain complexes IV and V. An age-related increase of carbonyl levels was found for aconitase and ATP synthase. [source]

The role of NGF uptake in selective vulnerability to cell death in ageing sympathetic neurons

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004
Kliment P. Gatzinsky
Abstract We have examined the hypothesis that differences in nerve growth factor (NGF) uptake and transport determine vulnerability to age-related neurodegeneration. Neurons projecting to cerebral blood vessels (CV) in aged rats are more vulnerable to age-related degeneration than those projecting to the iris. Uptake of NGF was therefore examined in sympathetic neurons projecting from the superior cervical ganglion (SCG) to CV and iris in young and old rats by treating the peripheral processes of these neurons with different doses of I125 -NGF. Total uptake of I125 -NGF was reduced in old CV-projecting, but not iris-projecting, neurons. Numbers of radiolabelled neurons projecting to each target were counted in sectioned ganglia. The data showed age-related reductions in numbers of labelled neurons projecting to CV, but no change in numbers of neurons projecting to the iris. Calculation of uptake of I125 -NGF per neuron unexpectedly showed no major age-related differences in either of the two neuron populations. However, uptake per neuron was considerably lower for young and old CV-projecting, compared to iris-projecting, SCG neurons. We hypothesized that variations in NGF uptake might affect neuronal survival in old age. Counts of SCG neurons using a physical disector following retrograde tracing with Fluorogold confirmed the selective vulnerability of CV-projecting neurons by showing a significant 37% loss of these neurons in the period between 15 and 24 months. In contrast, there was no significant loss of iris-projecting neurons. We conclude that vulnerability to, or protection from, age-related neurodegeneration and neuronal cell death are associated with life-long low, or high, levels of NGF uptake, respectively. [source]

Mitochondrial Oxidative Stress Plays a Key Role in Aging and Apoptosis

IUBMB LIFE, Issue 5 2000
Juan Sastre
Abstract Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the ageassociated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. [source]

Aging-Related Increase to Inducible Atrial Fibrillation in the Rat Model

Effect of aging on corticosterone secretion in diestrous rats

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006
Ming-Jae Lo
Abstract The roles of age and prolactin (PRL) in regulating glucocorticoid secretion in diestrous rats were investigated. Adrenal zona fasciculata-reticularis (ZFR) cells from young, adult, middle (mid)-aged, and old female rats were isolated. Estrous cycle stage was determined by light microscopy after vaginal smears. Blood samples were collected from right jugular vein at 0, 30, 60, and 120 min after challenge with adrenocorticotropin (ACTH). During the diestrous phase, plasma levels of estradiol and progesterone were lower in mid-aged and old rats than in either young or adult rats. Age-dependent increases of the basal levels of plasma PRL and corticosterone were observed. No difference of ACTH-increased plasma concentrations of corticosterone was observed among young, adult, mid-aged, and old rats. Aging increased the basal, ACTH-, PRL-, forskolin (an adenylate cyclase activator)-, and 3-isobutyl-l-methylxanthine (IBMX, a non-selective phosphodiesterase inhibitor)-stimulated release of corticosterone and production of adenosine 3,, 5,-cyclic monophosphate (cAMP) in ZFR cells. However, the 8-Br-cAMP (a membrane-permeable cAMP)-stimulated release of corticosterone was not affected by age. Taken together, these data indicated that aging increased corticosterone secretion in female rats during diestrous phase, which is in part due to an increase in cAMP accumulation. In conclusion, aging and PRL play a stimulatory role in the co-regulation of corticosterone secretion. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source]

Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008
Muyao Li
Advanced age is a major risk factor for atherosclerosis, but how aging per se influences pathogenesis is not clear. Insulin-like growth factor-1 receptor (IGF-1R) promotes aortic vascular smooth muscle cell (VSMC) growth, migration, and extracellular matrix formation, but how IGF-1R signaling changes with age in VSMC is not known. We previously found age-related differences in the activation of Akt/FOXO3a and ERK1/2 pathways in VSMC, but the upstream signaling remains unclear. Using explanted VSMC from Fischer 344/Brown Norway F1 hybrid rats shown to display age-related vascular pathology similar to humans, we compared IGF-1R expression in early passages of VSMC and found a constitutive activation of IGF-1R in VSMC from old compared to young rats, including IGF-1R expression and its tyrosine kinase activity. The link between IGF-1R activation and the Akt/FOXO3a and ERK pathways was confirmed through the induction of IGF-1R with IGF-1 in young cells and attenuation of IGF-1R with an inhibitor in old cells. The effects of three kinase inhibitors: AG1024, LY294002, and TCN, were compared in VSMC from old rats to differentiate IGF-1R from other upstream signaling that could also regulate the Akt/FOXO and ERK pathways. Genes for p27kip-1, catalase and MnSOD, which play important roles in the control of cell cycle arrest and stress resistance, were found to be FOXO3a-targets based on FOXO3a-siRNA treatment. Furthermore, IGF-1R signaling modulated these genes through activation of the Akt/FOXO3a pathway. Therefore, activation of IGF-1R signaling influences VSMC function in old rats and may contribute to the increased risk for atherosclerosis. J. Cell. Physiol. 217: 377,387, 2008. © 2008 Wiley-Liss, Inc. [source]

Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging

AGING CELL, Issue 2 2009
Sunitha Rangaraju
Summary Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo. Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy,lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health. [source]

Relative contribution of V-H+ATPase and NA+/H+ exchanger to bicarbonate reabsorption in proximal convoluted tubules of old rats

AGING CELL, Issue 5 2006
Mariana Fiori
Summary With aging, the kidney develops a progressive deterioration of several structures and functions. Proximal tubular acidification is impaired in old rats with a decrease in the activity of brush border Na+/H+ exchange and a fall of H-ion flux measured with micropuncture experiments. In the present work we evaluate the contribution of 5-N-ethyl-n-isopropyl amiloride- (EIPA) and bafilomycin-sensitive bicarbonate flux () in proximal convoluted tubules of young and aged rats. We performed micropuncture experiments inhibiting the Na+/H+ exchanger with EIPA (10,4 M) and the V-H+ATPase with bafilomycin (10,6 M). We used antibodies against the NHE3 isoform of the Na+/H+ exchanger and the subunit E of the V-H+ATPase for detecting by Western blot the abundance of these proteins in brush border membrane vesicles from proximal convoluted tubules of young and old rats. The abundance of NHE3 and the V-H+ATPase was similar in 18-month-old and 3-month-old rats. The bicarbonate flux in old rats was 30% lower than in young rats. EIPA reduced by 60% and bafilomycin by 30% in young rats; in contrast, EIPA reduced by ,40% and bafilomycin by ,50% in old rats. The inhibited by bafilomycin was the same in young and old rats: 0.62 nmol · cm,2· s,1 and 0.71 nmol · cm,2· s,1, respectively. However, the EIPA-sensitive fraction was larger in young than in old rats: 1.26 nmol · cm,2· s,1 vs. 0.85 nmol · cm,2· s,1, respectively. These results suggest that the component more affected in bicarbonate reabsorption of proximal convoluted tubules from aged rats is the Na+ -H+ exchanger, probably a NHE isoform different from NHE3. [source]

Reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat

AGING CELL, Issue 1 2003
T. Cowen
Summary Selective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT-PCR was used to examine NT expression in iris and CV in 3- and 24-month-old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT-PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris- compared with CV-projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV-projecting neurons at either age. However, similar treatment up-regulated p75 and trkA expression in iris-projecting neurons from 3-month-old, but not 24-month-old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age-related atrophy. [source]

Alteration in Hypothalamic Neuropeptide Y (NPY) Secretion May Underlie Female Reproductive Ageing: Induction of Steroid-Induced Luteinising Hormone Surge by NPY in Ovariectomised Aged Rats

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006
A. Sahu
A large body of evidence suggests that a defect in the hypothalamic function may be the primary cause of reproductive ageing in female rats. We have previously shown that luteinising hormone (LH)-surge associated changes in hypothalamic neuropeptide Y (NPY) gene expression and median eminence (ME) NPY levels seen in young rats do not occur in middle-aged (MA) rats. The present study examined whether hypothalamic NPY release is altered during the steroid-induced LH surge in ovariectomised (OVX) MA rats, and whether exogenous NPY initiates steroid-induced LH surge in OVX old rats. In the first study, NPY release from the ME-arcuate nucleus, as assessed by the push,pull cannula technique, was significantly increased before and during the progesterone-induced LH surge in oestrogen (E2)-primed ovariectomised young rats (2,3 months old). This antecedent increase in NPY release seen in young rats was not apparent in MA rats (11,13 months old) in association with a delayed and attenuated LH surge. In the second study, whereas progesterone failed to induce LH surges in E2 -primed ovariectomised old rats (23,25 months old), intracerebroventricular NPY (0.1,0.5 µg) injections at 1100, 1200 and 13.00 h resulted in LH surge induction in E2 + progesterone-primed ovariectomised old rats. Because increased hypothalamic NPY synthesis and release is obligatory for the preovulatory LH discharge in young rats, the present findings suggest that alteration in NPY release from the ME-arcuate nucleus contributes to the delayed and reduced LH surges in MA rats and may be involved in the subsequent loss of the LH surges in old rats. [source]

Young, adult, and old rats have similar changes in mRNA expression of many skeletal genes after fracture despite delayed healing with age

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2006
Ralph A. Meyer Jr.
Abstract Genes active in fracture healing are not well understood. Because age slows skeletal repair, the change in gene expression between animals of differing ages may illuminate novel pathways important to this healing response. To explore this, 6-, 26-, and 52-week-old female Sprague-Dawley rats were subjected to mid-diaphyseal femoral fracture with intramedullary fixation. The fracture callus was collected at 0, 0.4 (3 days), 1, 2, 4, or 6 weeks after fracture. RNA was extracted and pooled between two animals for each sample. Three samples were done for each time point for each age for a total of 54 Affymetrix U34A GeneChip microarrays. Of the 8700 genes on each array, 3300 were scored as present. Almost all of these genes were affected by femoral fracture with either upregulation or downregulation in the 6 weeks after fracture. Upregulated genes included markers for matrix genes for both cartilage and bone, osteoblasts, osteocytes, osteoclasts, fibroblasts, and mast cells. Downregulated genes included genes related to blood cell synthesis. Nearly all genes presently associated with bone metabolism showed the same response to fracture healing regardless of the age of the animal. In conclusion, skeletal fracture led to similar changes in RNA expression for most skeletal genes despite the delay in the formation of bone to bridge the fracture gap in old rats. Defects in the healing of skeletal trauma in older rats may lie in systems not normally studied by skeletal biologists. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1933,1944, 2006 [source]

Expression of N -methyl- D -aspartate (NMDA) and , -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) GluR2/3 receptors in the developing rat pineal gland

JOURNAL OF PINEAL RESEARCH, Issue 3 2005
C. Kaur
Abstract:, The expression of , -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate (GluR2/3) receptors and N -methyl- d -aspartate receptor subtype 1 (NMDAR1) was carried out by immunohistochemistry, double immunofluorescence and real-time RT-PCR analysis in the pineal glands of 1-day to 6-wk-old rats in the present study. GluR2/3 immunopositive cells were distributed throughout the pineal gland and showed branching processes in all age groups. The NMDAR1 immunoreactivity, however, was observed in fewer branched cells. A constitutive mRNA expression of NMDAR1, GluR2 and GluR3 was detected in the pineal glands of various ages and showed no significant difference between the age groups studied. Immunohistochemical and double immunofluorescence results showed that the GluR2/3 were mainly expressed and co-localized with OX-42-positive microglia/macrophages and the glial fibrillary acidic protein (GFAP)-positive astrocytes. Co-localization of NMDAR1 with OX-42- and GFAP-positive cells was much less. The expression of these receptors on the glial cells suggests that they may be involved in the development and growth of the pineal gland in the early postnatal period (1 day to 3 wk) and subsequently in the regulation of melatonin synthesis. [source]

The age-related decrease in CNS remyelination efficiency is caused by an impairment of both oligodendrocyte progenitor recruitment and differentiation

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2002
C. Zhao
Developing strategies to reverse the age-associated decline in CNS remyelination requires the identification of how the regenerative process is impaired. We have addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin-induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to PGDF-,R, and the OP transcription factor, MyT1. The expression patterns for both OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared to young. By comparing the mRNA expression pattern MyT1 with that of the myelin proteins MBP and Gtx, we have found that in the old animals there is also a delay in OP differentiation, which increases with longer survival times. These results indicate that the age-associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and their subsequent differentiation into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age-associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process. [source]

Evaluation of Baccharis trimera and Davilla rugosa in tests for adaptogen activity

PHYTOTHERAPY RESEARCH, Issue 6 2007
Fúlvio Rieli Mendes
Abstract Baccharis trimera (Asteraceae) and Davilla rugosa (Dilleniaceae) are used popularly as tonics, aphrodisiacs and for stomach ailments, among other uses. Hydroalcohol extracts of the aerial parts of both plants were investigated with regard to their chemical constitution and their pharmacological activity in tests that evaluate adaptogen activity. Alkaloids, flavonoids, saponins, polyphenols/tannins and coumarins were identified in both extracts, while lignans were found only in the extract of Davilla rugosa. This extract presented also a marked antioxidant activity and exerted a moderate antiulcer effect in rats submitted to cold immobilization stress. It did not, however, inhibit the increase in the levels of ACTH and corticosterone induced by stress. Moreover, the Davilla rugosa did not improve the physical performance of mice submitted to forced exercise and the learning time of old rats in the T-maze, neither did it reduce the blood viscosity of the old animals. Conversely, the Baccharis trimera extract only presented a moderate antioxidant activity, without any positive effect on the other tests. These results point to the absence of an adaptogen activity of Baccharis trimera, with some effects that could be related to such an activity as regards the Davilla rugosa. Copyright © 2007 John Wiley & Sons, Ltd. [source]

A role for leucine in rejuvenating the anabolic effects of food in old rats

THE JOURNAL OF PHYSIOLOGY, Issue 2 2005
Michael J. Rennie
No abstract is available for this article. [source]

Age-Related Three-Dimensional Morphological Changes in Rat Motoneurons Innervating Diaphragm and Longissimus Muscles

ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2008
H. Miyata
Summary We investigated age-related morphological changes of rat motoneurons innervating diaphragm muscle (DI-MN) and lumber longissimus muscle (LL-MN) in which quite different activation patterns exist. In young (2,4 months) and old (24,26 months) rats, the motoneurons innervating both muscles were labelled retrogradely by intramuscular injection of cholera toxin B subunit. After a 4-day survival, horizontal slices of the spinal cord were processed with immunohistochemical staining (first antibody to cholera toxin B subunit and second antibody with Cy3) and observed with a confocal microscope. Three-dimensional reconstruction of labelled motoneurons was performed to examine soma and dendrite morphology. As compared to the soma volume in young rats, significantly smaller values were found in old rats in both motoneurons and the degrees of decline were 16.1% in DI-MN and 20.3% in LL-MN. Significant decreases in the thickness of primary dendrites were also found in both motoneurons, and the degrees of decline were 17.5% in DI-MN and 22.3% in LL-MN. Smaller changes were found in DI-MN than in LL-MN, indicating the possibility that increased activation by central drives can attenuate age-related morphological changes of the motor system in the spinal cord. [source]

Vascular ,1 -adrenoceptors in isolated perfused rat kidney: influence of ageing

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2007
S. O. Awe
Summary 1 The present study identifies ,1 -adrenoceptor subtype(s) involved in constrictor responses of the kidney and how ageing influences it. 2 The study was conducted on kidneys from F344BNF1 rats, which unlike F344 or Wistar rats used by many previous investigators do not exhibit glomerulonephritis at advanced age. 3 Noradrenaline (NA) and phenylephrine (PHE) (non-selective ,1) and A61063 (selective ,1A) adrenoceptor agonists elicited constriction of perfused kidneys of young and old rats. The pD2 values (index of renovascular reactivity) were significantly higher for A61603 than for either PHE or NA, and significantly decrease across age groups. 4 BMY 7378 or RS 100329, ,1D - or ,1A -adrenoceptor antagonists, respectively antagonized the constrictor responses and suppressed the maximal responses to all agonists in young adult rat kidneys. However, antagonism of PHE or A61063 by BMY 7378 in old rat kidneys was surmountable. 5 This study suggests that: (i) ,1A and ,1D -adrenoceptor subtypes mediate vasoconstriction of perfused rat kidney; (ii) ,1A -adrenoceptor subtype appears to predominate in renal vasculature based on agonist relative potencies. (iii) Ageing significantly decreases ,1 -adrenoceptor-mediated vasoconstriction of rat kidney. [source]

Prostanoid release and constrictor responses to noradrenaline in the rat mesenteric vascular bed in non-insulin-dependent diabetes mellitus

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2001
H. A. Peredo
1,The administration of streptozotocin (STZ) to 2-day old rats induced a non-insulin-dependent diabetes mellitus (NIDDM)-like state, with mild hyperglycaemia and no alterations in body weight at the adult age. 2,In the isolated and perfused mesenteric vascular bed of NIDDM animals, the constrictor responses to either noradrenaline (NA) or potassium chloride (KCl) were not modified as compared with age-matched non-diabetic controls. 3,The reduction in NA contractions induced by the cyclooxygenase inhibitor, 10 ,M indomethacin in the control group was absent in the NIDDM rats. 4,The increase in the NA-induced contractions caused by endothelium removal was suppressed by indomethacin in the controls but not in the NIDDM group. 5,The prostanoid release from the mesenteric vascular beds of NIDDM rats was markedly reduced as compared with non-diabetic controls. Noradrenaline increased production of the constrictor prostaglandin (PG) F2, in control but not in NIDDM rats. 6,In summary, these results show that in STZ-induced NIDDM rats, there is an impairment of the prostanoid production, as well as a suppression of the role of prostanoids in the contractile effects of NA in the mesenteric vascular bed. These alterations are more severe than those previously observed in a model of insulin-dependent diabetes mellitus (IDDM), in which hyperglycaemia and reduction of body weight were more marked. The conclusion is that, in these models of diabetes and in the preparation studied, vascular alterations and modifications of glycaemia and body weight are not closely related. [source]

Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2005
Maria Álvarez De Sotomayor
The effects of oral administration of the HMG-CoA reductase inhibitor, simvastatin (SV), on age-related endothelial dysfunction were investigated in the aorta of male Wistar rats. Adult (12,14 weeks) and old (60,80 weeks) rats were treated daily for 12 weeks with either vehicle or SV (1 mg kg,1). In old rats, SV treatment did not significantly affect systolic blood pressure and LDL-cholesterol, but it reduced plasma cholesterol, triglycerides and oxidised LDL though it did not affect total antioxidant status. SV improved endothelium-dependent relaxation to acetylcholine and A-23187 in vessels from aged, but not adult, rats. This effect was linked to a greater NO vasodilatation via an increased expression of endothelial NO-synthase. A mechanism sensitive to superoxide dismutase and catalase also accounts for enhanced endothelial vasodilatation. Finally, SV did not affect the release of prostacyclin, but it inhibited the generation of thromboxane (TX) A2 from COX-2 isoform. The effect of the latter was sensitive to the Tp receptor antagonist, ICI-192,605. The present study provides evidence that oral administration of SV improves endothelial dysfunction in the aorta from aged rats by mechanisms associated with enhanced NO vasodilatation, reduced release of TXA2 from cyclo-oxygenase, and increased antioxidant properties of the vessel wall. These data underscore a new therapeutic perspective for SV in age-related endothelial dysfunction. British Journal of Pharmacology (2005) 146, 1130,1138. doi:10.1038/sj.bjp.0706420 [source]

Impact of ageing on the antinociceptive effect of reference analgesics in the Lou/c rat

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2002
Didier Jourdan
Research on the evolution of experimental pain perception and on the achievement of analgesia with ageing has led so far to contradictory results. This study investigated in the rat the impact of ageing on the antinociceptive effect of reference analgesics, acetaminophen (50, 100, 200, 400 mg kg,1 po), aspirin (50, 100, 200, 400 mg kg,1 sc), clomipramine (5, 10, 20, 40 mg kg,1 sc) and morphine (1.25, 2.5, 5, 10 mg kg,1 sc). Lou/c rats were chosen because they provide a model of healthy ageing and they do not develop obesity with age. Three groups of 40 rats each (mature (4 months), middle-aged (18 months) and old (26 months)), were treated with each drug at 14 days interval. Two tests were used: a thermal test (tail immersion in 48°C water and measurement of reaction latency) and a mechanical test (paw pressure and measurement of struggle threshold). Results confirm the increased mechanical sensitivity to pain and no change in thermal sensitivity for old rats compared to mature and middle-aged animals. They show a marked decrease in the effect of morphine with age and no age-related effect for acetaminophen, aspirin or clomipramine. Plasma levels of morphine and metabolites are not different in the three age groups. It is likely that the influence of age on morphine analgesia is linked mainly to pharmacodynamic rather than pharmacokinetic changes. British Journal of Pharmacology (2002) 137, 813,820. doi:10.1038/sj.bjp.0704944 [source]

AGE-RELATED SYNAPTIC CHANGES IN THE CA1 STRATUM RADIATUM AND SPATIAL LEARNING IMPAIRMENT IN RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2009
Li-Hong Long
SUMMARY 1Age-related impairments in hippocampus-dependent spatial learning and memory are not associated with a loss of neurons, but may be related to synaptic changes. In the present study, we analysed the behavioural performance of adult, middle-aged and old Wistar rats using the Morris water maze, as well as the structure of synapses and the expression of autophosphorylated Ca2+/calmodulin-dependent protein kinase II at threonine 286 (pThr286-,CaMKII), a key post-synaptic protein in the CA1 stratum radiatum, in the same rats. 2Old Wistar rats showed significant cognitive deficits. Synaptic density, the area of post-synaptic densities and the total number of synapses in the CA1 stratum radiatum of old rats were significantly decreased compared with adult rats. The decrease in autophosphorylated pThr286-,CaMKII was age dependent. 3These findings reveal that age-related impairments in learning and memory are associated with synaptic atrophy. The decreased expression of pThr286-CaMKII may result in reduced synaptic function with ageing. [source]