Studies on the novel effects of electron beam treated pollen on colony reproductive output in commercially-reared bumblebees (Bombus terrestris) for mass pollination applications.

Commercially-reared bumblebees provide an important pollinator service that helps support food production and security. The deployment of an appropriate non-thermal disinfection technology for the bulk treatment of pollen collected from honeybees for the feeding of commercial bumblebees is important in order to mitigate against complex diseases and unwanted pathogen spillover to native bees. High level disinfection of pollen was achieved using an electron (e)-beam dose of 100 kGy that corresponded to 78 % loss of cellular viability of bee pathogens before feeding to bumblebees as measured by the novel in vitro use of flow cytometry (FCM). Novel findings showed that e-beam treated-pollen that was fed to bumblebees produced fewer females, gynes and exhibited an absence of males when compared to control bumblebee colonies that were fed untreated commercial pollen. A similar trend emerged in bumblebee colony reproductive outputs when using membrane filtered washed pollen. Proteomic analysis of bumblebees from individual colonies fed with treated-pollen revealed a differential abundance of proteins associated with stress, immunity and metabolism when compared to the untreated pollen control group. Microbiome analysis of the bumblebee gut content revealed differences in microbiota between treated and untreated pollen in bumblebee colony studies. This novel study evaluated the impact of industrial e-beam treated-pollen on complex bee disease mitigation where physically treated-pollen fed to bumblebees was shown to substantially affect colony reproductive outputs.

The effects of cereal type and α-tocopherol level on milk production, milk composition, rumen fermentation, and nitrogen excretion of spring-calving dairy cows in late lactation.

Grass-based production systems use concentrate supplementation primarily when pasture quality and availability have declined. Barley is a common concentrate ingredient; however, oat grain grows well in Ireland, is a source of lipids and fiber, and may provide an alternative to barley. The antioxidant α-tocopherol (α-TOC) plays a role in cell membrane structure, and it has the potential to improve tight junction structures of the mammary gland that deteriorate in late lactation. The objective of this research was to investigate the effect of cereal type and α-TOC level on milk yield, milk composition, rumen fermentation, and N excretion in late-lactation dairy cows at pasture and when housed indoors on grass silage. Forty-eight Holstein Friesian dairy cows were blocked on days in milk (+185 d in milk) and balanced for parity, pre-experimental milk yield, milk composition, and body condition score and assigned to 1 of 4 dietary treatments in a randomized complete block design (n = 12). The dietary treatments were control (C) base diet; base diet + barley-based concentrate + low α-TOC (350 IU/kg) (B); base diet + oat-based concentrate + low α-TOC (350 IU/kg) (O); and base diet + oat-based concentrate + high α-TOC (1,050 IU/kg) (O+T). Following a 14-d acclimation period, diets were offered for a 49-d experimental period at pasture (P1) and a 21-d experimental period indoors (P2). The base diet was grazed grass in P1 and grass silage in P2. In P2, cows on C also received 2.65 kg (dry matter) of a standard concentrate. In P1, supplementation increased milk and milk solids yield (B: 20.7 kg/d, 1.74 kg/d; O: 20.6 kg/d, 1.81 kg/d; O+T: 20.5 kg/d, 1.77 kg/d, respectively) compared with C (17.8 kg/d, 1.60 kg/d). Cows offered B had a lower milk fat (4.60%) concentration than C (5.00%) and O (4.90%). In P2, cereal type and α-TOC level did not alter milk production. In conclusion, concentrate supplementation increased milk and milk solids yield and cows offered O had a higher milk fat concentration than cows offered B. Increasing the level of α-TOC had no major effect on production parameters measured in P1 or in P2.

The effect of concentrate supplementation type on milk production, dry matter intake, rumen fermentation, and nitrogen excretion in late-lactation, spring-calving grazing dairy cows.

In Ireland, milk is primarily produced using a spring-calving grass-based system, with the use of concentrate supplementation mainly when pasture availability and quality are reduced. In the autumn, when cows are in late lactation, reduced pasture productivity results in reduced milk yield and altered milk composition. Nitrogen utilization efficiency also reduces as lactation progresses. Concentrate supplementation has been found to increase milk production and reduce nitrogen (N) excretion, as high-N grass is usually replaced by a lower-N supplement; however, there is a paucity of information with regard to the optimum type of supplementation in late lactation. Therefore, the objective of this research is to investigate the effect of different concentrate supplementation types, based on barley or maize, on milk production, dry matter intake (DMI), rumen fermentation, and N excretion in late-lactation, spring-calving, grazing dairy cows. Thirty-six Holstein Friesian dairy cows were blocked on days in milk (185 DIM) and balanced for parity, pre-experimental milk yield, milk composition, and body condition score. Cows were randomly assigned to 1 of 3 dietary treatments in a randomized complete block design (n = 12). The 3 treatments consisted of a perennial ryegrass-based pasture-only (PO) treatment and pasture plus either of 2 supplementary concentrates, based on barley (PB) or maize (PM). The diets were fed for a 14-d acclimatization period and then for a further 63-d experimental period. Cows offered PO had a lower daily milk yield (15.1 kg) than PB (18.2 kg) or PM (16.8 kg). Similarly, PO had lower daily milk solids yield (1.46 kg) than PB or PM (1.68 and 1.53 kg, respectively). Cows offered PB had a greater milk yield and higher fat and protein yields than those offered PM. Offering PB increased total DMI (19.5 kg) compared with PO (17.7 kg), and milk response to concentrates was also greater for PB compared with PM (1.21 vs. 0.71 kg of milk per kg of concentrate). Cows offered PB had increased N in milk compared with PO. In conclusion, concentrate supplementation based on barley or maize resulted in increased milk and milk solids yield compared with offering PO. Cows offered barley had a greater response to concentrates and increased milk and milk solids yield in comparison to maize and showed increased N partitioning in milk compared with PO. A barley-based concentrate increased total DMI compared with PO.

Distress in patients with bleeding disorders: a single institutional cross-sectional study.

INTRODUCTION: Distress may affect a patient's ability to cope with and manage disease. AIM: To report distress prevalence in adult patients with bleeding disorders and determine whether specific clinical and health characteristics, including disease severity and employment status, are associated with distress. METHODS: Patients who visited a Haemophilia Treatment Centre (HTC) between January 1st, 2012 through February 28th, 2014 and who completed a distress screen, pain screen and questionnaire were evaluated cross sectionally. Distress was measured by the National Comprehensive Cancer Network Distress Management Tool, which allowed patients to rate recent distress on a 0-10 point scale. A rating of five or more was categorized as high distress. Pain was measured by the Brief Pain Inventory Short Form, which asked patients to rate pain types on 0-10 point scales. Patients reported employment and other demographic and behavioural information on the questionnaire. Primary diagnosis, age, HIV and HCV status were abstracted from medical records. Adjusted logistic regression was used to identify distress associations. RESULTS: High distress prevalence among 152 patients with bleeding disorders was 31.6%. Unemployment, disability, greater depressive symptoms and higher pain were associated with high distress in multivariable models. Bleeding disorder diagnosis, race/ethnicity, HIV/HCV status and on-demand treatment regimen were not associated with high distress. CONCLUSION: Distress among patients with congenital bleeding disorders followed at a comprehensive HTC was high and similar to that reported among patients with cancer. Future research should determine whether distress impacts clinical outcomes in patients with bleeding disorders as demonstrated in other chronic disorders.

Comparison of a semiautomated hand-held device to test minimal erythema dose before narrowband ultraviolet B phototherapy with the conventional method using matched doses.

BACKGROUND: A semiautomated hand-held device has been introduced in some phototherapy centres to establish the minimal erythema dose (MED) before treatment with narrowband ultraviolet (NBUV) B. OBJECTIVES: To compare the semiautomated hand-held device with the conventional method of MED testing (a UV-opaque template and a panel of UVB fluorescent tubes), using the same series of incremented doses. METHODS: Twenty-four patients referred for treatment with NBUVB phototherapy were included. Each patient had MED testing with the conventional method and the semiautomated hand-held device at the same level of the left and right back. The results were read by four investigators each time. RESULTS: The semiautomated hand-held device was a significant estimator of the MED using the conventional panel method (P < 0.001; r = 0.97). The average ratio of the hand-held MED to the conventional MED was 67%. The mean difference between the methods was 165 mJ/cm(2) . The interobserver test showed very high agreement for both methods of MED testing (Cronbach α coefficient 0.97 for the hand-held MED tester vs. 0.93 for the conventional method). CONCLUSIONS: The semiautomated hand-held device MED results were lower than that of the conventional panel method and may prolong the treatment course by 2-3 treatments. The hand-held tester is a fast and reproducible method, and may allow more phototherapy units, limited by staff and time, to do MED testing.

Comparison of a wheat-based diet supplemented with purified {beta}-glucans, with an oat-based diet on nutrient digestibility, nitrogen utilization, distal gastrointestinal tract composition, and manure odor and ammonia emissions from finishing pigs.

It was hypothesized that supplementation of an oat-extracted mixed-linkage (1 → 3), (1 → 4)-ß-d-glucan (ß-glucans) to a wheat-based diet may beneficially mitigate manure odor and ammonia emissions associated with intensive pig production, without depressing nutrient digestibility as has been observed with oat-based diets. An experiment was conducted to investigate the effect of dietary ß-glucan source and the inclusion of an enzyme composite containing ß-glucanase on energy and nutrient digestibility, N utilization, distal gastrointestinal tract (GIT) fermentation, and manure emissions from finisher boars. Twenty-eight boars (BW = 74.2 ± 3.6 kg) were assigned to 1 of 4 dietary treatments (n = 7/treatment): 1) an oat-based diet (oat), 2) an oat diet + enzyme composite (OE), 3) a wheat-based diet + purified ß-glucans (WG), and 4) a wheat-based diet + purified ß-glucans + enzyme composite. The wheat-based diets containing purified ß-glucans were formulated to contain concentrations of total ß-glucans comparable with the oat-based diet. Consumption of the WG diet resulted in a greater digestibility of GE (P = 0.001) and an increase in the urine:feces N excretion ratio (P = 0.049) compared with the oat diet. In the distal GIT, pigs offered the WG diet contained fewer bifidobacteria (P = 0.027) and lactobacilli (P = 0.050) compared with the oat diet. Pigs offered the WG diet had increased manure odor emissions compared with the oat diet (P = 0.023). In conclusion, although supplementing wheat-based diets with extracted oat-ß-glucan did not reduce nutrient digestibility, there was a negligible effect in beneficially influencing manure emissions from pigs when compared with a conventional oat formulation.

Effect of beta-glucans contained in barley- and oat-based diets and exogenous enzyme supplementation on gastrointestinal fermentation of finisher pigs and subsequent manure odor and ammonia emissions.

The objective of the current experiment was to evaluate the influence of dietary cereal sources of beta(1,3)(1,4)-d-glucan (beta-glucan) and enzyme supplementation on indices of environmental pollution from finisher pigs. An experiment with a 2 x 2 factorial arrangement of treatments was initiated to investigate the effect of dietary source of beta-glucan (barley vs. oats) and enzyme supplementation (no vs. yes) on nutrient digestibility, N utilization, intestinal fermentation, and manure odor and ammonia emissions from finisher boars (n = 4; BW = 73.9 kg; SD = 4.7). Sixteen boars were assigned to 1 of 4 dietary treatments (n = 4/treatment): 1) barley-based diet, 2) barley-based diet + exogenous enzyme, 3) oat-based diet, and 4) oat-based diet + enzyme. The enzyme supplement used contained endo-1,3(4)-beta-glucanase and endo-1,4-beta-xylanase. Experimental diets were formulated to contain similar concentrations of DE (13.5 MJ/kg) and digestible lysine (8.8 g/kg). Pigs offered oat-based diets had reduced digestibility of DM (0.795 vs. 0.849; SEM 0.007; P = 0.001), OM (0.808 vs. 0.865; SEM 0.007; P = 0.001), GE (0.806 vs. 0.845; SEM 0.006; P = 0.002), and NDF (0.233 vs. 0.423; SEM 0.033; P < 0.003) compared with those offered barley-based diets. Oat-based diets increased populations of Bifidobacterium spp. (7.26 vs. 6.38 log cfu/g of digesta; SEM 0.201; P = 0.005) and Lactobacillus spp. (6.99 vs. 6.18 log cfu/g of digesta; SEM 0.234; P = 0.022) in the proximal colon and decreased manure odor emissions [2,179.6 vs. 4,984.6 Ou(E)/m(3) (where Ou(E) refers to European odor units); SEM 653.7; P < 0.011] compared with barley-based diets. There was an interaction between cereal type and enzyme inclusion on manure ammonia emissions from 0 to 96 h (P = 0.050). Pigs offered barley-based diets containing an enzyme supplement had increased manure ammonia emissions compared with those offered unsupplemented barley-based diets. However, there was no effect of enzyme inclusion on oat-based diets. In conclusion, pigs offered oat-based diets harbored increased Bifidobacterium spp. and Lactobacillus spp. populations in the proximal colon and had decreased manure odor emissions compared with those offered barley-based diets. Enzyme inclusion had no effect on manure ammonia emissions from pigs offered oat-based diets.

Docosahexaenoic acid-induced changes in phospholipids in cortex of young and aged rats: a lipidomic analysis.

The age-related decline in cognitive function has been associated with biochemical changes that can be attenuated following n-3 polyunsaturated fatty acid treatment. Dietary supplementation with docosahexaenoic acid (DHA) has been shown to reverse age-related changes in synaptic function. Here, lipidomic analyses were undertaken to examine changes in lipid classes and phospholipid species in cortical tissue of young (2-4 months) and aged (20-22 months), control- and DHA-treated (10mg daily) rats following treatment for 8 weeks, aiming to explore the mechanism of DHA action. Dietary supplementation normalised the age-related decrease in unsaturation index, reduced the levels of arachidonic acid-containing phospholipids in both young and aged animals, and gave rise to production of new phosphatidylserine and phosphatidylinositol species. These findings suggest that DHA may mediate some of its effects through alterations in the membrane lipid composition that can consequently affect the production of pro-inflammatory mediators and signalling molecular species.

Preclinical science regarding cannabinoids as analgesics: an overview.

Modern pharmacology of cannabinoids began in 1964 with the isolation and partial synthesis of delta-9-tetrahydrocannabinol, the main psycho-active agent in herbal cannabis. Since then, potent antinociceptive and antihyperalgesic effects of cannabinoid agonists in animal models of acute and chronic pain; the presence of cannabinoid receptors in pain-processing areas of the brain, spinal cord and periphery; and evidence supporting endogenous modulation of pain systems by cannabinoids has provided support that cannabinoids exhibit significant potential as analgesics. The present article presents an overview of the preclinical science.

Guidelines for the use of cannabinoid compounds in chronic pain.

OBJECTIVE: To provide clinicians with guidelines for the use of cannabinoid compounds in the treatment of chronic pain. METHODS: Publications indexed from 1990 to 2005 in the National Library of Medicine Index Medicus were searched through PubMed. A consensus concerning these guidelines was achieved by the authors through review and discussion. RESULTS: There are few clinical trials, case reports or case series concerning the use of cannabinoid compounds in the treatment of chronic pain. There are no randomized clinical trials examining the use of herbal cannabis in the treatment of chronic pain. CONCLUSIONS: A practical approach to the treatment of chronic pain with cannabinoid compounds is presented. Specific suggestions about the off-label dosing of nabilone (Cesamet, Valeant Canada limitee/Limited) and dronabinol (Marinol, Solvay Pharma Inc, Canada) in the treatment of chronic pain are provided.

Patterns of cannabis use among patients with multiple sclerosis.

To estimate the patterns and prevalence of cannabis use among patients with multiple sclerosis (MS), 220 patients were surveyed in Halifax, Nova Scotia. Seventy-two subjects (36%) reported ever having used cannabis for any purpose; 29 respondents (14%) reported continuing use of cannabis for symptom treatment. Medical cannabis use was associated with male gender, tobacco use, and recreational cannabis use. The symptoms reported by medical cannabis users to be most effectively relieved were stress, sleep, mood, stiffness/spasm, and pain.

Adjunctive benefit of an essential oil-containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly: a six-month study.

BACKGROUND: Mechanical methods of oral hygiene can be complemented by the use of chemotherapeutic mouthrinses. The authors sought to quantify the additional benefit provided by an essential oil-, or EO-, containing mouthrinse in reducing plaque and gingivitis in patients who brush and floss regularly. METHODS: The authors randomly assigned patients with gingivitis to one of three treatment groups: brushing and rinsing with a control mouthrinse, or BC; brushing, flossing and rinsing with a control mouthrinse, or BFC; or brushing, flossing and rinsing with an EO-containing mouthrinse, or BFEO. Patients received a dental prophylaxis at baseline, and the authors followed them for six months. RESULTS: Of 246 enrolled subjects enrolled in the study, 237 subjects were evaluable at the study's conclusion. After six months, the subjects using the BFEO regimen had statistically and clinically significant lower mean Modified Gingival Index, or MGI, scores and Plaque Index, or PI, scores than did subjects in the BC group (29.9 percent and 56.3 percent, respectively; P < .001). Subjects in the BFC group had statistically significantly lower mean MGI and PI scores than did subjects in the BC group (11.2 percent and 9.3 percent, respectively; P < .001). Subjects in the BFEO group exhibited statistically and clinically significantly lower mean scores for MGI and PI than did subjects in the BFC group (21 percent and 51.9 percent, respectively; P < .001). CONCLUSIONS: This study confirms that for patients with gingivitis who brush and floss routinely, the adjunctive use of an EO-containing mouthrinse provides a clinically significant and meaningful additional benefit in reducing plaque and gingivitis. CLINICAL IMPLICATIONS: An EO-containing mouthrinse is an effective adjunct to regular brushing and flossing. Therefore, the BFEO regimen can be beneficial for patients with gingival inflammation.

A novel assay for discovery and characterization of pro-apoptotic drugs and for monitoring apoptosis in patient sera.

We have developed an apoptosis assay based on measurement of a neoepitope of cytokeratin-18 (CK18-Asp396) exposed after caspase-cleavage and detected by the monoclonal antibody M30. The total amount of caspase-cleaved CK18 which has accumulated in cells and tissue culture media during apoptosis is measured by ELISA. The sensitivity is sufficient for use in the 96-well format to allow high-through-put screening of drug libraries. We here describe strategies allowing classification of pro-apoptotic compounds according to their profiles of induction of apoptosis in the presence of pharmacological inhibitors. The time course of induction of CK18 cleavage can furthermore be used to distinguish structurally similar compounds. We propose that compounds that induce rapid CK18 cleavage have mechanisms of actions distinct from conventional genotoxic and microtubuli-targeting agents, and we present one example of an agent that induces almost immediate mitochondrial depolarization and cytochrome c release. Finally, CK18-Asp396 cleavage products are released from cells in tissue culture, and presumably from tumor cells in vivo. These products can be measured in sera from cancer patients. We present evidence suggesting that it will be possible to use the M30-ELISA assay for measuring chemotherapy-induced apoptosis in patient sera, opening possibilities for monitoring therapy.

Long-term potentiation in aged rats is restored when the age-related decrease in polyunsaturated fatty acid concentration is reversed.

Several age-related changes have been identified in rat hippocampus; among these are deficits in glutamate release and long-term potentiation in dentate gyrus. These deficits correlate with a decrease in the concentration of arachidonic acid in hippocampus. In this study, the effects of dietary supplementation for 8 weeks with omega -6 or omega -3 fatty acids were assessed in groups of aged and young rats. The data presented indicate that dietary supplementation in aged rats restored the concentrations of arachidonic acid and docosahexanoic acid in hippocampal preparations to those observed in tissue prepared from young rats. In parallel, aged rats which received the experimental diets sustained long-term potentiation in a manner indistinguishable from young rats. The evidence presented supports the view that an age-related increase in reactive oxygen species production is linked with the decrease in polyunsaturated fatty acids and that a diet enriched in eicosapentanoic acid has antioxidant properties which may play a key role in reversal of the observed age-related deficits.

Limb volume reduction after physical treatment by compression and/or massage in a rodent model of peripheral lymphedema.

Lack of a standardized experimental counterpart of peripheral lymphedema (LE) in a small animal has hampered research into treatment of this debilitating condition. We recently refined a rodent model consisting of radical unilateral lymphatic/nodal groin excision in conjunction with a circumferential integumental gap, followed by regional irradiation of the groin to reproduce stable unilateral hindlimb LE (1). In the current study, Wistar-Fuzzy rats with established right hindlimb LE, were subdivided into five groups and subjected to one of the following daily physical regimens over a 5-day period: pneumatic compression pumping at 30 torr (PCP); low-stretch multi-layered compressive bandaging using Coban (CB); manual lymphedema drainage (MLD) or a light massage consisting of stationary circular motions using the fingertips; combined physiotherapy (CPT consisting of MLD + CB); and a no treatment or control group (CTRL). Hindlimb and LE volumes were serially measured before and after treatment. Whereas CTRL showed progressive worsening of hindlimb swelling, PCP, CB, CPT and MLD each produced similar and substantial edema reduction over the 5 day interval, PCP, CB and CPT induced vacillating edema reduction which, however, exceeded rebound swelling on a daily basis. MLD, on the other hand, showed a steady gradual daily decline in LE volume.

Effect of dietary α-tocopherol supplementation on color and lipid stability in pork.

Myoglobin and lipid oxidation are major causes of quality deterioration in fresh pork. A process to enhance color and lipid stability would prove valuable to the pork industry given the current trend of centralized packaging and distribution to retail markets. Our objective was to determine the effects of dietary α-tocopherol (α-Toc) supplementation on color and lipid stability in ground pork, and loin chops stored in modified atmosphere packaging (MAP). Yorkshire crossbred pigs (n=20) were randomized into two groups and fed diets containing 48 (CON) or 170 mg α-Toc acetate/kg feed (VIT-E) for 6 weeks before slaughter. Plasma α-Toc concentration was measured weekly. Post-slaughter, Boston butt shoulders were ground, formed into patties with or without 1.5% salt, and stored fresh at 4°C for 0, 2, 4, or 6 days, and frozen at -20°C for 45 or 90 days. Pork loin chops were packaged aerobically and stored at 4°C for 0, 2, 4 or 6 days, or in MAP at 4°C for 7, 10 or 13 days prior to Hunter L*,a*,b* and TBARS analyses. α-Toc concentration of longissimus dorsi, psoas major, biceps femoris, semimembranosus and semitendinosus muscles was determined. Plasma α-Toc was greater (P<0.05) in VIT-E animals compared with CON and α-Toc concentrations were greater (P<0.05) in all VIT-E muscles compared with CON. TBARS values of both fresh and salted patties were less in VIT-E than in CON meat following 6 days at 4°C; VIT-E TBARS of salted patties were less (P<0.05) after 45 days at -20°C compared with CON. α-Toc supplementation did not influence (P>0.05) color of aerobically packaged or MAP chops, or of fresh or salted pork patties. α-Toc supplementation reduced TBARS formation in fresh and salted pork but had no significant impact on color.

The inhibitory effect of interleukin-1beta on long-term potentiation is coupled with increased activity of stress-activated protein kinases.

Long-term potentiation (LTP) in perforant path-granule cell synapses is decreased in aged rats, stressed rats, and rats injected intracerebroventricularly with the proinflammatory cytokine interleukin-1beta (IL-1beta). One factor that is common to these experimental conditions is an increase in the concentration of IL-1beta in the dentate gyrus, suggesting a causal relationship between the compromise in LTP and increased IL-1beta concentration. In this study, we have investigated the downstream consequences of an increase in IL-1beta concentration and report that the reduced LTP in rats injected intracerebroventricularly with IL-1beta was accompanied by a decrease in KCl-stimulated glutamate release in synaptosomes prepared from dentate gyrus, although unstimulated glutamate release was increased. These changes were paralleled by increased activity of the stress-activated kinases, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. Intracerebroventricular injection of IL-1beta increased reactive oxygen species production in hippocampal tissue, whereas IL-1beta and H(2)O(2) increased activities of both JNK and p38 in vitro. Dietary manipulation with antioxidant vitamins E and C blocked the increase in reactive oxygen species production, the stimulation of JNK and p38 activity, the attenuation of glutamate release, and the IL-1beta-induced inhibitory of LTP. We propose that IL-1beta stimulates activity of stress-activated kinases, which in turn may inhibit glutamate release and result in compromised LTP and that these actions are a consequence of increased production of reactive oxygen species.

Age-related impairment in LTP is accompanied by enhanced activity of stress-activated protein kinases: analysis of underlying mechanisms.

The age-related impairment in long-term potentiation in the rat dentate gyrus is coupled with an increase in the proinflammatory cytokine, interleukin-1beta (IL-1beta). It is possible that this increase in IL-1beta might be a consequence of the age-related increase in reactive oxygen species production in hippocampal tissue. In this study we set out to identify the underlying cause of the age-related increase in reactive oxygen species production and to establish whether any consequences of such a change might impact on the ability of aged rats to sustain long-term potentiation (LTP). We report that there was an age-related increase in the activity of superoxide dismutase but no parallel increases in activities of glutathione peroxidase or catalase, while age-related decreases in the concentration of the scavengers, vitamins E and C and glutathione were also observed. We propose that these compromises in antioxidative strategies may result in an increase in reactive oxygen species production. The data described indicate that IL-1beta and H2O2 increase the activity of two stress-activated mitogen-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 in vitro, while age-related increases in both kinases were observed. We propose that the endogenous increase in these parameters which occurs with age induces the increase in activity of the stress-activated kinases, which in turn impacts on the ability of the aged rat to sustain LTP.

Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids.

Depolarization-induced transmitter release in synaptosomes prepared from the hippocampus of aged rats is decreased compared with release from young animals. Although the underlying cause of this deficit is not known, some evidence suggests that increased membrane rigidity may contribute to these age-related synaptic changes. One possible consequence of the decreased transmitter release in the hippocampus of aged rats is a reduced ability to sustain long-term potentiation in perforant path-granule cell synapses, a pathway in which maintenance of long-term potentiation and increased glutamate release have been coupled. The observation that there is an age-dependent impairment in long-term potentiation is consistent with this view. If the age-related deficits in release and long-term potentiation are a consequence of increased membrane rigidity, it must be predicted that any manoeuvre which reverses membrane rigidity should reverse these functional deficits. In the present study, we investigated the effect of dietary manipulation of aged rats with omega-3 fatty acids on synaptic function. The data obtained indicate that an eight-week modified feeding schedule reversed the age-related impairments in long-term potentiation and depolarization-induced glutamate transmitter release. We also report that the concentrations of both docosahexanoic acid and arachidonic acid, two main polyunsaturated fatty acids in neuronal membranes, were decreased in the hippocampus of aged rats, and were restored by dietary manipulation. The data are consistent with the hypothesis that these deficits results from a change in membrane composition.