Effects of chronic cigarette smoke inhalation on the development of senile lung in senescence-accelerated mouse

The senescence-accelerated mouse (SAM) manifests most of the features of function and morphology in the senile lung with aging. However, little is known about the effects of age and cigarette smoke on alterations of the lung in SAM. In the present study, we examined the effects of chronic cigarette smoke inhalation and age on the function and morphology of lungs in two strains of SAM, SAMP2 (senescence-prone strain) and SAMR1 (senescence-resistant strain), from 6 months of age (young) and 18 months of age (aged). After 4 weeks of cigarette smoke inhalation, a small but significant airspace along with a leftward shift of the pressure-volume (P-V) curve was observed in young SAMP2, but not in SAMR1. However, the airspace size of young SAMP2 with cigarette inhalation was smaller than that in aged SAM with air inhalation, suggesting that the effect of age may be greater than that of the small burder of tobacco smoke on the lung alterations in SAMP2. In the aged SAM, there were no differences in function and structure between tobacco-exposed and air-exposed mice. Because the changes in the lungs of young SAMP2 exposed to cigarette smoke were partly simulated with age-related alterations in human lung, and because age-dependent changes of lungs were clearly investigated in SAMP2, this strain may be an interesting animal model for investigating the effects of age and/or cigarette smoke on alterations in lung structure and function.     

嗅三针对SAMP8小鼠海马磷酸化PI3K/Akt蛋白表达和突触可塑性的影响

目的:观察嗅三针对SAMP8小鼠海马磷酸化PI3K、Akt蛋白表达和海马突触可塑性损伤的影响,探讨嗅三针治疗阿尔茨海默病(AD)模型小鼠的作用机制。方法:将40只SAMP8小鼠随机分为模型组(Model)、嗅三针组(XSZ)、嗅神经切断嗅三针组(XSZ+XSJ)和盐酸多奈哌齐组(Donepezil),每组10只,10只SAMR1小鼠作为正常组(Control)。XSZ组和XSZ+XSJ组采用电针刺激印堂穴和双侧迎香穴,Donepezil组采用盐酸多奈哌齐灌胃,Control组和Model组不干预。采用Morris水迷宫实验评价小鼠学习记忆能力,新物体识别实验评价小鼠新物体识别能力,Western Blot和免疫组化检测小鼠海马区p-PI3K和p-Akt蛋白表达,透射电镜观测小鼠海马突触超微结构。结果:与Model组比较,XSZ和Donepezil干预均可以明显降低SAMP8小鼠4d平均逃避潜伏期,增加其靶象限停留时间、穿越平台次数和新物体偏爱指数,明显升高其海马p-PI3K和p-Akt蛋白表达(P<0.05),改善其海马神经元突触结构;XSZ+XSJ对于SAMP8小鼠学习记忆能力、新物体识别能力指标及p-PI3K、p-Akt蛋白表达无显著影响(P>0.05),对其突触结构损伤无明显改善;对于上述指标的影响,XSZ组与Donepezil组比较无显著差异(P>0.05)。结论:嗅三针可能基于嗅觉通路完整性,调节海马PI3K/Akt磷酸化表达,修复海马突触形态结构损伤,改善海马突触可塑性,从而发挥提高SAMP8小鼠学习记忆能力的效应。     

Tocotrienols reach the brain and play roles in the attenuation of body weight gain and improvement of cognitive function in high-fat diet-treated mice

Obesity induces severe disorders such as type 2 diabetes and cardiovascular events, and the number of people with obesity is increasing all over the world. Furthermore, it is possible that obesity increases the risk of cognitive dysfunction via the acceleration of oxidative damage. Tocotrienols, which are part of the vitamin E family, have antioxidant and anti-obesity effects. However, the effects of tocotrienols on high-fat diet-treated mice have not been completely elucidated. In this study, we assessed changes in body weight, spatial reference memory acquisition, liver lipid droplet size, blood brain barrier-related protein expressions and antioxidative defense systems in high-fat diet-treated mice in the presence or absence of tocotrienols. The results showed that tocotrienols significantly inhibited body weight gain and lipid droplet synthesis. Although the amount was very small, it was confirmed that tocotrienols surely reached the brain in the perfused brain. Treatment with tocotrienols was tended to improve cognitive function in the control mice. However, tocotrienols did not modulate blood brain barrier-related protein expressions or antioxidative defense systems. These results indicate that treatment with tocotrienols could be effective for the prevention of obesity and cognitive dysfunction. Further extended research is needed to elucidate the relationship between anti-obesity and antioxidant effects of tocotrienols, especially in the brain.     

Preliminary Clinical Evaluation of Toxicity and Efficacy of A New Astaxanthin-rich Haematococcus pluvialis Extract

Astaxanthin (Ax), a carotenoid ubiquitously distributed in microorganisms, fish, and crustaceans, has been known to be a potent antioxidant and hence exhibit various physiological effects. We attempted in these studies to evaluate clinical toxicity and efficacy of long-term administration of a new Ax product, by measuring biochemical and hematological blood parameters and by analyzing brain function (using CogHealth and P300 measures). Ax-rich Haematococcus pluvialis extracts equivalent to 4, 8, 20 mg of Ax dialcohol were administered to 73, 38, and 16 healthy adult volunteers, respectively, once daily for 4 weeks to evaluate safety. Ten subjects with age-related forgetfulness received an extract equivalent to 12 mg in a daily dosing regimen for 12 weeks to evaluate efficacy. As a result, no abnormality was observed and efficacy for age-related decline in cognitive and psychomotor functions was suggested.     

Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

Tempol intake improves inflammatory status in aged mice

Oxidative stress is associated with both healthy aging and age-related disease states. In connection with oxidative stress, immunity is also a major component as a result of the chronic, low-grade inflammation associated with the development of tissue aging. Here we show that long-term treatment with the antioxidant tempol extends life-span in mice. Tempol-treated mice exhibited a reduction in mortality at 20 months. Tempol drinking did not have any effect on body weight, amount of visceral adipose tissue, or plasma biochemical parameters in aged mice. Body temperature of aged control mice (which drank only water) was significantly lower than young mice, but this reduction of body temperature was partially restored in aged mice which drank tempol. Plasma thiobarbituric acid-reactive substances and C-reactive protein were significantly increased in the control aged mice compared with young mice, but levels of both were normalized by tempol drinking. One of the endogenous antioxidants, ascorbic acid, was significantly increased in the plasma of mice which consumed tempol. The proportion of CD4 lymphocytes in the blood of aged tempol-treated mice was partially increased in comparison to aged control mice. These results suggest that the reduction of mortality by tempol is due to amelioration of chronic inflammation and improved function of the immune system through antioxidant effects.     

The effects of aging on material-independent and material-dependent neural correlates of contextual binding

Previous behavioral research suggests that older adults exhibit impairments in source memory across a multitude of stimuli and associated details, possibly due to a deficit in contextual binding. However, it is unclear whether this binding deficit results from alterations in processes that are material-independent, processes that are specific to particular materials, or some combination of the two. We used event-related fMRI to investigate the effect of aging on contextual binding and associated neural activity for words and objects. Behavioral data showed similar age-related deficits in source memory accuracy for both words and objects. Imaging results revealed that young and older adults recruited similar networks of regions in support of contextual binding, independent of material, including the lateral prefrontal cortex (PFC) and hippocampus. Material-dependent binding effects were also present for both groups in ventrolateral prefrontal and parahippocampal cortices for words and objects, respectively. Older adults showed smaller material-independent contextual binding effects in frontal regions, namely the left dorsolateral PFC, and larger binding effects in the hippocampus. Further, age-related declines in object processing effects in extrastriate regions correlated with poorer source accuracy for objects. Collectively, these results suggest that age-related source memory deficits may be primarily due to changes in material-independent contextual binding processes. However, these impairments may be further impacted by impoverished item representations in material-specific processing regions.     

Melatonin attenuates cognitive dysfunction and reduces neural oxidative stress induced by phosphamidon

Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)-treated group at weeks 6 and 8 as compared to the control group. Two-week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP-SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.     

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

There is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elderly is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this exploratory multi-center study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goal-directed attention.     

Beyond age and gender: relationships between cortical and subcortical brain volume and cognitive-motor abilities in school-age children

There is growing evidence that cognitive and motor functions are interrelated and may rely on the development of the same cortical and subcortical neural structures. However, no study to date has examined the relationships between brain volume, cognitive ability, and motor ability in typically developing children. The NIH MRI Study of Normal Brain Development consists of a large, longitudinal database of structural MRI and performance measures from a battery of neuropsychological assessments from typically developing children. This dataset provides a unique opportunity to examine relationships between the brain and cognitive-motor abilities. A secondary analysis was conducted on data from 172 children between the ages of 6 to 13 years with up to 2 measurement occasions (initial testing and 2-year follow-up). Linear mixed effects modeling was employed to account for age and gender effects on the development of specific cortical and subcortical volumes as well as behavioral performance measures of interest. Above and beyond the effects of age and gender, significant relationships were found between general cognitive ability (IQ) and the volume of subcortical brain structures (cerebellum and caudate) as well as spatial working memory and the putamen. In addition, IQ was found to be related to global and frontal gray matter volume as well as parietal gray and white matter. At the behavioral level, general cognitive ability was also found to be related to visuomotor ability (pegboard) and executive function (spatial working memory). These results support the notion that cognition and motor skills may be fundamentally interrelated at both the levels of behavior and brain structure.     

Promoting a brain-healthy lifestyle

The population of older adults is increasing worldwide. Old age is often associated with a continuous decline in memory and along with other forms of cognitive decline can impede the self-management abilities necessary for everyday functioning. Recent research suggests that adapting a brain-healthy lifestyle may reduce age-related cognitive decline and, in some instances, improve memory and thinking. As a health educator the gerontological nurse can help older people to navigate the information essential to improving brain health. Nurses can incorporate knowledge about brain-healthy behaviours into older adults' routines.     

Shape variability of the human striatum--Effects of age and gender

Human striatum is involved in the regulation of movement, reinforcement, learning, reward, cognitive functioning, and addiction. Previous classical volumetric MRI studies have implicated age-, disease- and medication-related changes in striatal structures. Yet, no studies to date have addressed the effects of these factors on the shape variability and local structural alterations in the striatum. The local alterations may provide meaningful additional information in the context of functional neuroanatomy and brain connectivity. We developed image analysis methodology for the measurement of the volume and local shape variability of the human striatum. The method was applied in a group of 43 healthy controls to study the effects of age and gender on striatal shape variability. In the volume analysis, the volume of the striatum was normalized using the volume of the whole brain. In the local shape analysis, the deviations from a mean surface were studied for each surface point using high-dimensional mapping. Also, discriminant functions were constructed from a statistical shape model. The accuracy and reproducibility of the methods used were evaluated. The results confirmed that the volume of the striatum decreases as a function of age. However, the volume decrease was not uniform and age-related shape differences were observed in several subregions of the human striatum whereas no local gender differences were seen. Examination of the variability of striatal shape in the healthy population will pave the way for applying this method in clinical settings. This method will be particularly useful for investigating neuropsychiatric disorders that are associated with subtle morphological alterations of the brain, such as schizophrenia.     

Effectiveness of Hydrogen Rich Water on Antioxidant Status of Subjects with Potential Metabolic Syndrome—An Open Label Pilot Study

Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5–2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55–0.65 mM), by the following chemical reaction; Mg + 2H₂O → Mg (OH)₂ + H₂. The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.     

Delivery across the blood-brain barrier of antisense directed against amyloid beta: reversal of learning and memory deficits in mice overexpressing amyloid precursor protein

Amyloid beta protein (Abeta) may play a causal role in Alzheimer's disease. Previous work has shown that the learning and memory deficits that develop with aging in SAMP8 mice, a strain that overproduces Abeta, can be reversed with i.c.v. injections of an Abeta antisense phosphorothiolate oligonucleotide (Olg). Here, we showed that Olg radioactively labeled with (32)P (P-Olg) was transported intact across the blood-brain barrier (BBB) of mice by a saturable system, termed oligonucleotide transport system-1 (OTS-1). Multiple-time regression analysis found a blood-to-brain unidirectional influx rate for P-Olg of 1.4 +/- 0.39 microl/g-min and capillary depletion showed that P-Olg completely crossed the BBB to enter the parenchymal space of the brain. P-Olg was also shown to enter the cerebrospinal fluid. Transport was especially high into the hippocampus, with the percentage of the i.v. dose taken up by each gram of brain (0.865 +/- 0.115%) being about 1/100 of the i.c.v. dose. An i.v. dose of Olg 100 times that of the effective i.c.v. dose reversed the learning and memory deficits of aged SAMP8 mice. These studies show for the first time that phosphorothiolate oligonucleotides can be delivered to the brain in effective doses by intravenous administration.     

Morning Cortisol Levels and Cognitive Abilities in People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study

OBJECTIVE

People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study of 1,066 men and women aged 60–75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.

RESULTS

In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).

CONCLUSIONS

High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes.Type 2 diabetes is associated with cognitive impairments, including deficits in processing speed, executive function and declarative memory, and with structural changes in the brain including reductions in hippocampal and amygdalar volumes, which are key areas influencing learning and long-term memory (1,2). Hyperglycemia, cerebral microvascular disease, and recurrent severe hypoglycemic episodes have all been implicated as potential causative factors of cognitive decline (3) but are unlikely to explain the entire effect of diabetes on cognition.Increasing evidence supports a link between elevated plasma glucocorticoids and cognitive dysfunction. Exogenous glucocorticoid administration and elevated endogenous glucocorticoids (as occurs in Cushing''s syndrome) are associated with cognitive impairment in animals and humans. More subtle alterations in hypothalamic-pituitary-adrenal (HPA) axis function have also been linked with cognitive function, with higher plasma cortisol levels at 0900 h being associated with poorer age-related cognitive ability in a small group of elderly, healthy male volunteers (4). Conversely, manipulations that reduce plasma glucocorticoid concentrations or their effects on target tissues can attenuate cognitive decline with ageing in rodents (5,6). Elevated glucocorticoid levels have widespread effects within the central nervous system, including deleterious effects on the structure and function of the hippocampus, a key locus for cognitive function, which also highly expresses glucocorticoid receptors (7,8).Several studies have demonstrated that people with type 2 diabetes have activation of the HPA axis, manifested by elevated basal plasma cortisol levels (9,10), higher late-night salivary cortisol levels (11), elevated ACTH levels (12), increased cortisol levels following overnight dexamethasone suppression (13,14), and impaired habituation of cortisol levels to repeated stress (15). These findings are consistent with a central dysregulation of the HPA axis in type 2 diabetes. The elevated plasma cortisol levels are associated with metabolic abnormalities in diabetes (16) and with complications of diabetes, including retinopathy, neuropathy, and nephropathy (17).Investigators have started to explore whether altered HPA axis activity contributes to cognitive impairment in diabetes. Impaired central negative feedback control of the HPA axis, as indicated by higher cortisol levels after 1.5 mg dexamethasone administration, was related to declarative memory impairments, possibly reflecting hippocampal dysfunction, in 30 individuals with type 2 diabetes compared with age-, sex-, and education-matched control subjects (18). However, the association between cortisol and cognitive function disappeared after adjustment for glycemic control (A1C). The same investigators reported similarly impaired HPA axis feedback control in association with verbal declarative memory deficits in 41 subjects with type 2 diabetes (1). In the latter study, the subjects with type 2 diabetes also had reduced hippocampal and prefrontal volumes, but there were no significant associations between the cortisol measurements and magnetic resonance image findings (1).Despite these findings from animal and human studies, information from large-scale epidemiological studies of representative populations is lacking, which could confirm or refute an association between circulating plasma cortisol levels and age-related cognitive impairment. We therefore examined the relationship between fasting cortisol and both late-life cognitive ability and estimated lifetime cognitive change in a large, representative study population of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study [ET2DS]). The ET2DS has the advantage over many previous epidemiological studies of having detailed cognitive testing in a range of cognitive domains and very extensive phenotyping for potential confounding or mediating factors.     

The selective M1 muscarinic cholinergic agonist CDD-0102A enhances working memory and cognitive flexibility

Various neurodegenerative diseases and psychiatric disorders are marked by alterations in brain cholinergic function and cognitive deficits. Efforts to alleviate such deficits have been limited by a lack of selective M(1) muscarinic agonists. 5-(3-Ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A) is a partial agonist at M(1) muscarinic receptors with limited activity at other muscarinic receptor subtypes. The present studies investigated the effects of CDD-0102A on working memory and strategy shifting in rats. CDD-0102A administered intraperitoneally 30 min before testing at 0.1, 0.3, and 1 mg/kg significantly enhanced delayed spontaneous alternation performance in a four-arm cross maze, suggesting improvement in working memory. In separate experiments, CDD-0102A had potent enhancing effects on learning and switching between a place and visual cue discrimination. Treatment with CDD-0102A did not affect acquisition of either a place or visual cue discrimination. In contrast, CDD-0102A at 0.03 and 0.1 mg/kg significantly enhanced a shift between a place and visual cue discrimination. Analysis of the errors in the shift to the place or shift to the visual cue strategy revealed that in both cases CDD-0102A significantly increased the ability to initially inhibit a previously relevant strategy and maintain a new, relevant strategy once selected. In anesthetized rats, the minimum dose required to induce salivation was approximately 0.3 mg/kg i.p. Salivation increased with dose, and the estimated ED(50) was 2.0 mg/kg. The data suggest that CDD-0102A has unique memory and cognitive enhancing properties that might be useful in the treatment of neurological disorders at doses that do not produce adverse effects such as salivation.     

铅与幼鼠脑组织蛋白激酶 C活性及记忆功能改变的关系

背景铅暴露引起的动物学习记忆障碍与脑细胞中蛋白激酶 C(protein kinase C,PKC)活性改变是否有关系呢? 目的研究慢性铅暴露下发育期小鼠大脑组织 PKC活性变化规律及其对小鼠记忆发育的影响. 设计以实验动物为研究对象,随机对照的验证性实验研究. 单位卫生部细胞生物学重点实验室. 材料实验在中国医科大学生物化学与分子生物学实验室完成.选择五六周龄昆明种小白鼠 72只. 方法以不同浓度的醋酸铅饲喂交配后的雌鼠,其幼崽通过哺乳和直接饮水接触铅.在幼崽生后 1 d( P1), 8 d( P8), 15 d( P15), 22 d( P22), 30 d( P30)将其分别处死,取出脑组织.采用 [γ 32P]ATP放射性磷标记法于体外测定铅暴露小鼠大脑组织的 PKC的活性;另外取暴露于不同浓度醋酸铅的发育期小鼠,通过被动回避反应实验进行记忆行为学训练和测试,观察不同浓度的铅对小鼠记忆的影响. 主要观察指标①不同浓度铅暴露对发育期小鼠大脑组织内 PKC活性的影响.②不同浓度铅暴露对发育期小鼠记忆行为的影响. 结果对幼鼠脑 PKC的活性测定显示在发育初期铅暴露小鼠脑中 PKC活性高于正常,发育后期则低于正常,高浓度铅对 PKC活性抑制较强;记忆行为学测试可见低浓度铅使小鼠发育初期记忆曲线升高,而使中长期记忆曲线减低;铅浓度升高,记忆曲线降低. 结论铅对小鼠大脑组织中 PKC活性发育有抑制作用,铅浓度越高,抑制越明显;低浓度铅在短时间内似有刺激记忆的作用,长时间低浓度铅暴露使记忆抑制;高浓度铅使记忆能力降低作用更明显.铅对发育期小鼠脑中 PKC活性及记忆功能的影响有一定的相关性.     

Intermolecular hydrogen bonds between catechin and theanine in tea: slow release of the antioxidant capacity by a synergetic effect

The health benefits of drinking tea stem from it being rich in polyphenols and other physiologically-active substances. Thus, exploring the synergistic effect between polyphenols and a variety of physiologically-active substances can contribute to our understanding of how tea benefits health. In this work, we have studied the interactions between catechin and theanine, exploring the synergetic antioxidant mechanism of the two molecules. Electrochemical characterization results showed that the oxidation peak current of catechin decreased gradually with the concentration of theanine, which is due to theanine spontaneously binding to catechin through intermolecular hydrogen bonds and forming molecular clusters via two hydrogen bonds. The binding constant is 4.75 at room temperature. The molecular clusters reduce the diffusion coefficient of catechin in solution, leading to the slow release of its antioxidant capacity (ability to effectively inhibit free radical oxidation reactions). Density functional theory calculations were also performed and verified the binding behavior. In identifying the synergistic effect between catechin and theanine on the antioxidant capacity of tea, this study adds to our understanding of the efficacy of tea polyphenols.

The health benefits of drinking tea stem from it being rich in polyphenols and other physiologically-active substances.     

Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice

Exenatide is a potent and selective agonist for the GLP‐1 (glucagon‐like peptide‐1) receptor. Recent studies are focused on the effects of GLP‐1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 μg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ‐NA)‐induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain‐derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real‐time polymerase chain reaction (RT‐PCR). This study revealed that in the mEPM and PA tests, type‐2 diabetes‐induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP‐1 receptor agonist exenatide. Quantitative RT‐PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA‐induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder.