Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice

Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety- and depression-like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4−/−) mice with control and germ line Y2−/− animals. Anxiety- and depression-like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress-induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4−/− and Y2−/− mice exhibited reduced anxiety-related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4−/− but reduced in Y2−/− mice. The basal rectal temperature exhibited diurnal and genotype-related alterations. Control mice had temperature minima at noon and midnight, whereas Y4−/− and Y2−/− mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4−/− and Y2−/− mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2−/− but not in Y4−/− mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety-like and depression-related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.     

Omega-3 fatty acids from fish oils and cardiovascular disease

Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA/DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA/DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA/DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA/DHA in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease. (Mol Cell Biochem 263: 217–225, 2004)     

Determination of the rate of K movement through potassium channels in isolated rat heart and liver mitochondria

Both ATP-regulated (mitoK_ATP) and large conductance calcium-activated (mitoBK_Ca) potassium channels have been proposed to regulate mitochondrial K⁺ influx and matrix volume and to mediate cardiac ischaemic preconditioning (IP). However, the specificity of the pharmacological agents used in these studies and the mechanisms underlying their effects on IP remain controversial. Here we used increasing concentrations of K⁺-ionophore (valinomycin) to stimulate respiration by rat liver and heart mitochondria in the presence of the K⁺/H⁺ exchanger nigericin. This allowed rates of valinomycin-induced K⁺ influx to be determined whilst parallel measurements of light scattering (A₅₂₀) and matrix volume (³H₂O and [¹⁴C]-sucrose) enabled rates of K⁺ influx to be correlated with increases in matrix volume. Light scattering readily detected an increase in K⁺ influx of < 5 nmol K⁺ min^− 1 per mg protein corresponding to < 2% mitochondrial matrix volume increase. In agreement with earlier data no light-scattering changes were observed in response to any mitoK_ATP channel openers or blockers. However, the mitoBK_Ca opener NS1619 (10-50 µM) did decrease light scattering slightly, but this was also seen in K⁺-free medium and was accompanied by uncoupling. Contrary to prediction, the mitoBK_Ca blocker paxilline (10-50 µM) decreased rather than increased light scattering, and it also slightly uncoupled respiration. Our data argue against the presence of significant activities of either the mitoK_ATP or the mitoBK_Ca channel in rat liver and heart mitochondria and provide further evidence that preconditioning induced by pharmacological openers of these channels is more likely to involve alternative mechanisms.     

Impact of [d-Lys3]-GHRP-6 and feeding status on hypothalamic ghrelin-induced stress activation

Ghrelin administration directly into hypothalamic nuclei, including the arcuate nucleus (ArcN) and the paraventricular nucleus (PVN), alters the expression of stress-related behaviors. In the present study we investigated the effect of feeding status on the ability of ghrelin to induce stress and anxiogenesis. Adult male Sprague Dawley rats were implanted with guide cannula targeting either the ArcN or PVN. In the first experiment we confirmed that ArcN and PVN ghrelin treatment produced anxiety-like behavior as measured using the elevated plus maze (EPM) paradigm. Ghrelin was administered during the early dark cycle. Immediately after microinjections rats were placed in the EPM for 5 min. Both ArcN and PVN treatment reduced open arm exploration. The effect was attenuated by pretreatment with the ghrelin 1a receptor antagonist [d-Lys³]-GHRP-6. In a separate group of animals ghrelin was injected into either nucleus and rats were returned to their home cages for 60 min with free access to food. An additional group of rats was returned to home cages with no food access. After 60 min with or without food access all rats were tested in the EPM. Results indicated that food consumption just prior to EPM testing reversed the avoidance of the open arms of the EPM. In contrast, rats injected with ghrelin, placed in their home cage for 60 min without food, and subsequently tested in the EPM, exhibited an increased avoidance of the open arms, consistent with stress activation. Overall, our findings demonstrate that ghrelin 1a receptor blockade and feeding status appear to impact the ability of ArcN and PVN ghrelin to elicit stress and anxiety-like behaviors.     

Fertility,Inheritance and Amino Acid Analysis of Lysine Plus Threonine-Resistant Mutant Progenies of Maize

Sixth generation of mutant maize seed homozygous for lysine plus threonine resistancewhich was derived from the resistant callus cultures has been harvested. The resistance could be inherited stably. The fertility, however, was very poor. The resistant homozygotes have been obtained by backcross of the wild type with the resistant plants (W77-R3019 ×R0), and their fertility could be parlty recovered after selection for the resistant plants from backcross progenies. Genetic analysis showed that the resistance inherited as a single dominant nuclear allele. All of the free amino acids except phenylalan inc in the homozygote are increased by 4 folds. and free essential amino acids by 5 folds which are higher than those in the wild types. Total amino acids increased by 5.53%. The dramatic increase (11 times) in free threonine adds up the total threonine by 17.73%. Difference of the protein content between the homozygote and wild type was not obvious. These results show that selection for the resistance to lysine plus threonine in maize and other cereals is probably very useful for improving their value of protein nutrition.