Groups Of Aged Rats Research Articles

Supplementation of complex milk lipid concentrate (CMLc) improved the memory of aged rats

ObjectivesThe socio-economic impact from age-related mental decline is escalating. Supplementation of functional foods for sustaining mental health is desirable. We examined the effect of long-term supplementation of complex milk lipid concentrate (CMLc), mixed dairy phospholipids, on memory and associated vascular and neuronal changes in aged rats.MethodsFisher/Norway Brown rats were used. Two groups of aged rats (24 months) were fed with either gelatin-formulated CMLc or blank gelatin as the control, for 4 months. To determine age-related changes, a young group (5 months) was also fed with blank gelatin. Morris water maze tests were carried out after the supplementation and brain tissues were collected for biological analysis.ResultsThe aged control rats learnt to locate the platform slower than the young control rats during acquisition trials (*P < 0.05), and made fewer entries to and more initial heading errors from the platform zone during testing trials (*P < 0.05). The CMLc supplementation improved memory by showing the reduced initial heading errors in a delayed probe trial (#P < 0.05). We also found that the aged rats with CMLc supplementation improved vascular density, dopamine output, and neuroplasticity (#P < 0.05) in the brain regions involved in memory compared with that of the aged control rats.DiscussionThe data suggested that the supplementation of CMLc during the early stage of brain aging may prevent memory decline possibly through improving vascular and neuronal function.

Role of some selected Bifidobacterium strains in modulating immunosenescence of aged albino rats

Probiotic administration has been associated with enhanced immune function in elderly subjects. However, approaches for selection of an “ideal” strain of bifidobacteria are still difficult. The aim of the present study is to investigate the possible modulatory effects of three strains of Bifidobacterium species ( Bifidobacterium adolescentis ATCC 15704, Bifidobacterium breve ATCC 15700 and Bifidobacterium longum ATCC 15707) on haematological and immunological parameters of aged albino rats corresponding to normal adult ones. The animals were divided into six groups; three groups of aged rats were fed yoghurt inoculated with one of the Bifidobacterium strains; one group of aged rats was fed yoghurt alone (control aged); two groups of adult and aged rats were provided with normal diet and assigned as normal groups. The total leucocyte count was significantly increased in the three bifidobacteria-treated aged groups as compared with both normal and control aged rats. Serum IgA level was considerably increased in all treated rats. On the contrary, serum IgE level was significantly decreased in rats supplemented with yoghurt inoculated with B. adolescentis or B. breve . Both B. adolescentis and B. breve groups showed significant enhanced production of TNF-α. Furthermore, the production of cytokine IL-8 was significantly increased in the B. adolescentis group. Interestingly, it was apparent that only B. adolescentis had the most pronounced effect on aged rats to regain nearly normal values as measured in normal adult rats. Conclusively, the present work indicates that dietary consumption of selected bifidobacteria strains may have a particular application in the elderly especially in terms of immunomodulation.

Quercetin Flavonoid Has In Vivo Antioxidant Properties By Increasing Hepatic Expression Of Gpx And Hepatic Gpx Enzyme Activity In Old Rats

BackgroundQuercetin, one of the major flavonoids present in the human diet, has been associated with a wide range of biological properties, including antioxidant, anti‐inflammatory and anticarcinogenic actions. The antioxidant action is considered as the most likely mechanism for the beneficial effects of quercetin. However, little is known on its activity in vivo. Therefore, the present study aimed to investigate the in vivo effects of quercetin on mRNA and activity levels of hepatic GSTa2 in aged rats. This study was carried out on 28 male Wistar albino rats of 24‐months age. Rats were allocated into 2 groups: 1‐Quercetin treated group (14 rats): Received Quercetin (50 mg/kg by gavage for 7 days). 2‐Control group (14 rats): Received 1 ml/kg distilled water by gavage for 7 days.ResultsQuercetin treatment resulted in significant increase in relative hepatic mRNA levels for glutathione peroxidase (GPx) and liver GPx enzyme activity (1.67 ± 0.78 versus 1 ± 0.05, p&lt; 0.01 and 375.92±27.84 versus 242.78 ±19.79 mU/mg protein, p&lt;0.01 respectively). On the other hand, it significantly decreased relative hepatic mRNA levels for Gsta2, hepatic GST enzyme activity and hepatic glutathione concentrations (0.45 ± 0.16 versus 1 ± 0.04, p&lt; 0.01, 127.78±12.9 versus 181.85±17.23 mU/mg protein, p&lt;0.01 and 19.55 ±3.96 versus 23.78 ± 3.28, p&lt;0.01 respectively). No significant difference was found in BMI or in plasma concentration of ox‐LDL between the two groups of aged rats.ConclusionOur results indicate that quercetin flavonoid has in vivo antioxidant properties by increasing hepatic expression of GPx and hepatic GPx enzyme activity in old rats.

Low intensity laser therapy accelerates muscle regeneration in aged rats

Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels. Moreover, capillary blood count was more prominent in elderly rats in laser irradiated groups when compared to young animals. In conclusion, LILT increased the maturation of satellite cells into myoblasts and myotubes, enhancing the regenerative process of aged rats irradiated with laser.

Concurrent hippocampal induction of MHC II pathway components and glial activation with advanced aging is not correlated with cognitive impairment

BackgroundAge-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half of the aged population. Induction of a variety of neuroinflammatory measures has been reported with brain aging but the relationship between neuroinflammation and cognitive decline with non-neurodegenerative, normative aging remains largely unexplored. This study sought to comprehensively investigate expression of the MHC II immune response pathway and glial activation in the hippocampus in the context of both aging and age-related cognitive decline.MethodsThree independent cohorts of adult (12-13 months) and aged (26-28 months) F344xBN rats were behaviorally characterized by Morris water maze testing. Expression of MHC II pathway-associated genes identified by transcriptomic analysis as upregulated with advanced aging was quantified by qPCR in synaptosomal fractions derived from whole hippocampus and in hippocampal subregion dissections (CA1, CA3, and DG). Activation of astrocytes and microglia was assessed by GFAP and Iba1 protein expression, and by immunohistochemical visualization of GFAP and both CD74 (Ox6) and Iba1.ResultsWe report a marked age-related induction of neuroinflammatory signaling transcripts (i.e., MHC II components, toll-like receptors, complement, and downstream signaling factors) throughout the hippocampus in all aged rats regardless of cognitive status. Astrocyte and microglial activation was evident in CA1, CA3 and DG of intact and impaired aged rat groups, in the absence of differences in total numbers of GFAP+ astrocytes or Iba1+ microglia. Both mild and moderate microglial activation was significantly increased in all three hippocampal subregions in aged cognitively intact and cognitively impaired rats compared to adults. Neither induction of MHCII pathway gene expression nor glial activation correlated to cognitive performance.ConclusionsThese data demonstrate a novel, coordinated age-related induction of the MHC II immune response pathway and glial activation in the hippocampus, indicating an allostatic shift toward a para-inflammatory phenotype with advancing age. Our findings demonstrate that age-related induction of these aspects of hippocampal neuroinflammation, while a potential contributing factor, is not sufficient by itself to elicit impairment of spatial learning and memory in models of normative aging. Future efforts are needed to understand how neuroinflammation may act synergistically with cognitive-decline specific alterations to cause cognitive impairment.

Influence of late-life exposure to environmental enrichment or exercise on hippocampal function and CA1 senescent physiology

Aged (20–22 months) male Fischer 344 rats were randomly assigned to sedentary (A-SED), environmentally-enriched (A-ENR), or exercise (A-EX) conditions. After 10–12 weeks of differential experience, the 3 groups of aged rats and young sedentary controls were tested for physical and cognitive function. Spatial discrimination learning and memory consolidation, tested on the water maze, were enhanced in environmentally-enriched compared with sedentary. A-EX exhibited improved and impaired performance on the cue and spatial task, respectively. Impaired spatial learning in A-EX was likely due to a bias in response selection associated with exercise training, as object recognition memory improved for A-EX rats. An examination of senescent hippocampal physiology revealed that enrichment and exercise reversed age-related changes in long-term depression (LTD) and long-term potentiation (LTP). Rats in the enrichment group exhibited an increase in cell excitability compared with the other 2 groups of aged animals. The results indicate that differential experience biased the selection of a spatial or a response strategy and factors common across the 2 conditions, such as increased hippocampal activity associated with locomotion, contribute to reversal of senescent synaptic plasticity.

Age-Dependent Availability and Functionality of Bone Marrow Stem Cells in an Experimental Model of Acute and Chronic Myocardial Infarction

The aim of this study was to investigate the effect of aging and timing of left ventricular ischemic injury on the availability and functionality of stem cells. We studied young and aged male inbred Lewis rats that were used as donors of bone marrow mononuclear cells (BM-MNCs), divided in four experimental groups: controls, sham operated, 48 h post-myocardial infarction (MI), and 28 days post-MI. In vitro studies included flow cytometry analysis, hematopoietic colony-forming capacity, and invasion assays of migration capacity. BM-MNCs from these groups were transplanted in female rats after MI induction. Late engraftment was evaluated by real-time PCR of the SRY chromosome. Percentage of CD34+/CD45+(low) cells was similar among different experimental groups in young rats, but was significantly higher in aged animals (p < 0.001), particularly 28 days post-MI. KDR+/CD34+ cells were increased 48 h after MI and decreased 28 days post-MI in young animals, while they were profoundly reduced in the aged group (p < 0.001). Triple staining for CD44+/CD29+/CD71+ cells was similar in different groups of aged rats, but we observed an intense increase 48 h post-MI in young animals. Colony-forming units and cytokine-induced migration were significantly attenuated 28 days after the MI. Late engraftment in infarcted transplanted female hearts was present, but considerably heterogeneous. Finally, recovery of left ventricular systolic function in transplanted female recipients was significantly influenced by donors' BM-MNCs groups (p < 0.01). We have demonstrated that aging and timing of myocardial injury are factors that may act synergistically in determining stem cell availability and function. Such interaction should be considered when planning new cell therapy strategies for acute and chronic ischemic heart disease in the clinical arena.

Toxic effects caused by rhubarb (Rheum palmatum L.) are reversed on immature and aged rats

Rhubarb is generally used to people of broad age, but diverse responses of people at different age to rhubarb have been little clarified. In this study, an attempt was made to access the safety of rhubarb to both immature and aged rats to provide some references for its clinical usage. The total extract of rhubarb was administered intragastricly to both immature and aged rats once a day and lasted for 5 weeks. Then histopathologic and biochemical examinations were performed. No death was observed in immature rat groups, while 23.3% (21/90) subjects in aged rat groups died and most of the death cases were observed in the high-dosage (40 gkg(-1) of body weight per day od, counted on the quantity of crude material) group. The death rate between aged and immature rats was found of significantly statistical difference. Dosage-dependent histopathologic changes in kidney were observed in all the rhubarb-treated rats, principally involving the proximal tubules. Kidney changes in aged rats were severer than those observed in immature ones. Hepatic cells necrosis was occasionally observed in the middle- and high-dosage aged rat groups and minimal biliary hyperplasia was found in all the rhubarb-treated aged rats. Increased incidences of activated Kupffer cells and lymphocytic infiltration were found in all the rhubarb-treated rats. And dosage-dependent increase of interleukin 6 (IL-6) and notable increase of IL-8 was found in aged rat groups. The immature and aged rats showed reversed responses to the toxic potential of rhubarb extract. Elderly subjects were susceptible to the toxicity of high-dosage rhubarb, which drove rigorous consideration on rational use of rhubarb to aged people.

Age-related changes in the central auditory system: Comparison of d-galactose-induced aging rats and naturally aging rats

One of the most common complaints among aging individuals is difficulty in understanding speech in a compromised listening environment, such as when background noise is present. Age-related hearing loss (presbycusis) is associated with both peripheral and central neural processing deficits, as it occurs even in those with only a mild peripheral hearing impairment. The current study was designed to investigate potential causative mechanisms of this impairment by using a rat model in which presbycusis is inducible by administration of d-galactose ( d-gal). One group of these rats was injected subcutaneously with 150 mg d-gal daily for 8 weeks, while control animals received vehicle only. These groups were compared to naturally aged rats (24 months) that had received no other treatment. Central auditory function of the three groups was evaluated by measuring the auditory brainstem response (ABR) and middle latency response (MLR). A TaqMan real time PCR assay was used to quantify a 4834-bp deletion in the mitochondrial DNA (mtDNA) of the auditory cortex (AC), inferior colliculus (IC) and cochlear nucleus (CN). We assessed changes in lipid peroxidation levels and apoptosis rates, and examined pathological changes corresponding to d-gal-induced aging and natural aging. Both groups of aged rats exhibited delayed ABR latencies (III, IV, V), MLR Pa latency, and I-IV interpeak latency. Moreover, increased mtDNA 4834 bp deletion rates, lipid peroxidation levels, rates of neuronal apoptosis and neurodegenerative changes in the AC, IC and CN were similar among the d-gal induced and NA rats. However, the threshold of ABR in the d-gal group showed no significant change from the control group. These observations suggest that age-related central auditory dysfunction and its corresponding pathological changes are present in both naturally aging rats and the d-gal mimetic aging model. Oxidative stress, large-scale mtDNA 4834 bp deletion, and apoptosis are likely to be involved in the progressive weakening of the central auditory system associated with the aging process.

Anti-Aging Effects of Nanpao®, a Kampo Medicine, on Reproductive Functions in Female Rats

The improvement effect of nanpao, a kampo medicine, on the age-related decline in reproductive function was evaluated in female rats given the test drug for a long-term period. Young rats were allocated to the cesarean section and natural delivery groups to examine reproductive performance (young rat groups). Five-month-old rats were allocated to the 3 groups (aged rat groups): 1--control and 2--nanpao-treated groups. They were given orally in a dose of 0, 30 or 100mg/kg/day of the test drug, respectively. In aged rats, the first mating experiment was initiated at week 21 of dosing to evaluate reproductive performance by natural delivery and the second mating experiment at week 31 of dosing was evaluated by cesarean section. In the first and second mating experiments, various reproductive functions decreased in aged rats as compared to the young rats. On the other hand, loss of regular estrous cycles, decreases in delivery and pregnancy rates and mean fetal weights were inhibited in the treated groups as compared to the control group. In addition, decreases in the numbers of mean live offspring and fetuses were inhibited in the 100 mg/kg/day group. In conclusion, nanpao maintained normal embryo-foetal development in female rats.

Effect of lipid-based suspension of Epimedium koreanum Nakai extract on sexual behavior in rats

Ethnopharmacological relevance Herba of Epimedium koreanum is used in traditional Chinese and Korean herbal medicine as a potent enhancer of erectile function. Icariin, the main active component of Epimedium koreanum, possesses many biological effects, such as improving cardiovascular function, hormone regulation, immunological function modulation, and anti-tumor activity. Aim of the Study This study supports the traditional use of extracts from Epimedium species in erectile dysfunction. Materials and Methods The Epimedium koreanum dry extract was suspended in wheat germ oil using lecithin and bee wax for oral administration. The effect of oral administration of two compositions (E-01 and E-02) standardized by their icariin content on the number of complete intromissions, the number of ejaculations, and the latent period of ejaculation (LPE) in rats were evaluated. E-01 and E-02 were administered orally for 10 days to the experimental animals. The control animals received olive oil for 10 days. On day 10, 0.5 h after the dose was administered to male rats, one virgin female rat was placed with one male rat. Results The number of complete intromissions increased to 23.3 ± 2.6 in the E-01 and E-02 group (dose 300 mg/kg body weight) (b.wt) and to 20.1 ± 2.3 in the E-02 group (dose 750 mg/kg b.wt) compared with 15.2 ± 2.4 in the control group of aged rats. The number of ejaculations increased from 1.1 ± 0.3 in the control-aged group to 2.6 ± 0.4 in the E-01 group. The LPE of male rats was 14.2 ± 1.8 min in the control-aged group. The LPE of the aged group was reduced to 9.8 ± 1.5 min, 9.8 ± 1.6 min, and 11.4 ± 1.8 min when treated with E-01 at a dose of 300 mg/kg b.wt, and E-02 at a dose of 300 mg/kg b.wt and 750 mg/kg b.wt, respectively. Conclusion It was established that oral administration of lipid-based suspension of dry extract of Epimedium koreanum in wheat germ oil improved erectile function of aged rats.

The role of growth hormone and amino acids on brain protein synthesis in aged rats given proteins of different quantity and quality

The purpose of the present study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentrations of insulin and growth hormone (GH), and whether the concentrations of amino acids in the brain and plasma regulate the brain protein synthesis when the quantity and quality of dietary protein is manipulated. Two experiments were done on three groups of aged rats given diets containing 20% casein, 5% casein or 0% casein (Experiment 1), and 20% casein, 20% gluten, or 20% gelatin (Experiment 2) for 1 d (only one 5-h period) after all rats were fed the 20% casein diet for 10 d (only 5-h feeding per day). The aggregation of brain ribosomes, the concentration in plasma GH, and the branched chain amino acids in the plasma and cerebral cortex declined with a decrease of quantity and quality of dietary protein. The concentration of plasma insulin did not differ among groups. The results suggest that the ingestion of a higher quantity and quality of dietary protein increases the concentrations of GH and several amino acids in aged rats, and that the concentrations of GH and amino acids are at least partly related to the mechanism by which the dietary protein affects brain protein synthesis in aged rats.

Effects of lipids and aging on the neurotoxicity and neuronal loss caused by intracerebral injections of the amyloid-β peptide in the rat

The influence of diet and age on the area of lesion and on the neuronal density in the cerebral cortex was studied in rats following local injections of the amyloid-β peptide (Aβ1–40) in PBS vehicle into the left frontal and cingulate cortices and compared with effects of injections of PBS alone into the corresponding regions of the right hemisphere The experiments were carried out in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control group. In order to evaluate the interaction of Aβ/PBS-cholesterol and of Aβ/PBS-fat, animals without dietary manipulation receiving Aβ and PBS injection were used as controls. The results showed that the greatest area of lesion was at Aβ injection sites in the high-cholesterol fed group of aged animals. The results also revealed a significant variance in the neuronal density by group and by injection type. Thus, high-cholesterol fed animals showed a greater reduction in neuronal density at Aβ and PBS-injected sites than that seen in the high-fat or control groups. The results also indicate that the loss of neurons at the Aβ injection site exceeds that seen in the PBS-injected area. The greatest reduction in the neuronal density was found at Aβ-injected site in the high-cholesterol fed group of aged animals. In conclusion, our findings indicate an interaction between lipids, age, and Aβ neurotoxicity, and might provide insights into the basic mechanisms involved in a short-term (acute-to-subchronic) response to Aβ peptide.

Amyloid beta peptide-induced cholinergic fibres loss in the cerebral cortex of the rat is modified by diet high in lipids and by age

The influence of diet and age on the effects of intracerebral injection of beta-amyloid peptide (Aβ1–40) in vehicle phosphate-buffered saline (PBS) and on the effects of vehicle alone on cholinergic fibres of the cerebral cortex was studied in rats. The experiments were carried in two groups of animals: one group of young adult rats and a second group of aged rats. Each group of animals, depending on the diet received, was divided into high-cholesterol, high-fat, and a control diet group. In order to evaluate the interaction of Aβ/PBS-cholesterol and of Aβ/PBS-fat, animals without dietary manipulation receiving Aβ and PBS injection were used as controls. High-cholesterol fed animals showed a statistically significant reduction of 49.62% in the number of cholinergic fibres at the Aβ injection site as compared with that at PBS injection site, while the high-fat and control animals showed a significant reduction of 28.13 and 26.81%, respectively. In all diet groups, the loss of cholinergic fibres caused by Aβ as compared to that caused by PBS injection was significantly greater in aged rats in comparison with that observed in the young animals. Furthermore, the results of a multivariate linear regression model revealed that the greatest reduction in cholinergic fibres was in the high-cholesterol fed animals (35 fibres/mm) as compared with that seen in the high-fat and control animals. A significantly greater reduction was also observed at Aβ injection site (28 fibres/mm) as compared with that caused by PBS injection, and a reduction of 16 cholinergic fibres per mm was found in aged animals as compared to that seen in young adult rats. These results show that high-cholesterol diet enhances the toxicity of Aβ peptide and that this is also age-dependent. Therefore, this study increases the evidences of the role of cholesterol in the pathology of Alzheimer's disease (AD).

Age-related sex differences in spatial learning and basal forebrain cholinergic neurons in F344 rats

Basal forebrain cholinergic neurons are important for spatial learning in rodents. Spatial learning ability is reportedly better in males than females, and declines with age. To examine the role of cholinergic function in sex- or age-related differences in spatial learning, we compared the size of basal forebrain cholinergic neurons (BFCN) of young and aged male and female Fischer 344 (F344) rats that had been trained in the Morris water maze. Young male and female rats were equally proficient in finding the platform during training trials, but probe tests revealed that young male rats had better knowledge of the platform's precise location. Impairments in spatial learning were observed in aged rats, and the advantage of males over females was lost. BFCN were significantly larger in young male than young female rats, and were correlated with spatial memory performance for both groups. BFCN were smaller in aged than young males; no change was seen between young and aged females. In the groups of aged rats the correlation between neuron size and spatial memory was lost. The present findings provide further evidence of a role for the basal forebrain cholinergic system in spatial learning, but reveal a complex interaction between sex, age and behavioral performance.

Synaptic plasticity preserved with arachidonic acid diet in aged rats

We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 μm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus.

Effect of increased dietary selenium intake on blood and cardiac selenium status during aging in rats

Oral selenium supplementation has been described as cardioprotective against pathophysiological situations involving oxidative stress in young adults rats. However no data are available concerning the effects of selenium supplementation on selenium status and glutathione peroxidase (GPX) activity in senescent rats. In the present study young adult and senescent rats were fed a diet containing selenium either 0.05 mg/kg (control) or 1.5 mg/kg (selenium) for 10 weeks. Selenium content in both diets was adjusted by sodium selenite addition. At the end of the supplementation period although plasma selenium level was lower in the two groups of aged rats than in the corresponding adults (p < 0.05), cardiac GPX activity, measured in both cytosolic and mitochondrial extracts appeared to be similarly increased in both categories of age. These data are the first to indicate that oral Se-supplementation is able to increase the plasma selenium concentration and cardiac GPX activity in senescent rats as well as in young adults.

Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands.

In humans, nicotine has been demonstrated to improve both normal and disordered attention, suggesting potential clinical utility for nicotinic ligands. However, attempts to replicate these findings in the rodent have met with some difficulty, thus hampering the search for specific receptor mechanisms underlying these effects. In the present studies, we sought to characterize the effects of nicotine and subtype-selective ligands in a group of aged rats, which show consistent deficits in sustained attention over prolonged sessions of responding in the five-choice serial reaction time task (5-CSRTT). Following the establishment of a replicable performance improvement with nicotine (0.4 mg/kg), we assessed the effects of both SIB 1765F (1-5 mg/kg) and AR-R17779 (20 mg/kg), agonist ligands with selective affinities for the alpha(4)beta(2) and alpha(7) receptor sites, respectively. We then attempted to block this effect of nicotine using the high affinity, competitive nicotinic antagonist DHbetaE (3 mg/kg). Finally, in an attempt to determine whether the psychostimulant profile of nicotinic agonists could be dissociated from their effects on attention, we compared the (R)- and (S)-enantiomers of SIB 1765F in the 5-CSRTT, and in their ability to increase locomotor activity. Reversal of a within-session decline in performance speed and accuracy by nicotine was mimicked by SIB 1765F, but not by AR-R17779, whereas DHbetaE antagonized all of the performance changes induced by nicotine. Finally, the (S)- but not the (R)-enantiomer increased locomotor activity and improved performance in the 5-CSRTT. These results support a critical involvement for the alpha(4)beta(2) nicotinic receptor in mediating the attention-enhancing properties of nicotine.

Lack of effects of oxolinic acid on spermatogenesis in young adult and aged Wistar rats

Prolonged treatment with oxolinic acid is known to elevate serum luteinizing hormone (LH) levels, resulting in induction of Leydig cell tumors in rats. In a carcinogenicity study of the compound, tubular atrophy of the testis was also increased, suggesting that oxolinic acid might affect spermatogenesis. The present study was therefore performed using rats of different ages with a particular focus on seminiferous tubule alteration and its relation to Leydig cell proliferation. Young adult (7 weeks of age) and aged (52 weeks of age) males of the Wistar strain were administered oxolinic acid at dietary concentrations of 0 (basal diet), 300, 1000 or 3000 ppm for 4 (all groups), 13 (0 and 3000 ppm groups), 26 (0 and 3000 ppm groups), or 52 weeks (0 and 3000 ppm groups of aged rats). Serum LH levels were elevated in both young adult and aged animals treated with 3000 ppm at most examined time points. While testosterone levels were also increased at the early time points in young adult, this was not the case in older animals. Elevation of the incidences of foci and/or focal hyperplasia of Leydig cells was noted but was only slight limited to aged rats treated with 3000 ppm after 26 weeks. Furthermore, it did not appear to be related to seminiferous tubular alteration. No treatment-related histopathological abnormalities could be detected in any treatment group, and morphometrical stage analysis of spermatogenesis conducted for the control and 3000 ppm-treated groups demonstrated no lesions. These results provide strong evidence that prolonged oxolinic treatment does not directly induce testicular toxicity or altered spermatogenesis in either young adult or aged rats, except for slight increase of Leydig cell proliferative lesions caused by elevated serum LH levels. Aged rats might have higher sensitivity than young adults to the effects of oxolinic acid on proliferative lesions of Leydig cells.

Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination

The ladder rung walking test is a new task to assess skilled walking and measure both forelimb and hindlimb placing, stepping, and inter-limb co-ordination. Rats spontaneously walk from a starting location to a goal along a horizontal ladder. The spacing between the rungs of the ladder is variable and can be changed to prevent the animal from learning either the absolute or relative location of the rungs. The testing procedure requires minimal training and allows detailed quantitative and qualitative analysis using video recording. The utility of the test is described with postoperative data obtained from animals with unilateral neocortical strokes produced by pial stripping over the motor cortex, neonatal and adult unilateral corticospinal tract lesions produced by tract section at the pyramids, and unilateral dopamine depletions produced by injection of 6-hydroxydopamine into the nigrostriatal bundle. In addition, a group of aged rats was examined. Deficits in limb placing, stepping and co-ordination displayed by the animals demonstrate that this test can discriminate between lesions of the motor system or age-associated impairments. The test is useful for assessing loss and recovery of function due to brain or spinal cord injury, the effectiveness of treatment therapies, as well as compensatory processes through which animals adapt to nervous system injury.