饮食热能限制对脑老化小鼠学习记忆及突触可塑性的影响

<正>热能限制(caloric restriction,CR)被称为衰老研究领域最重大的发现,即在满足机体对各种营养素需要量的前提下,适当限制食物摄入,又称饮食限制(dietary restriction,DR)。McCay等于1935年首次报道CR延长大鼠寿限,迄今70余年来,大量实验研究证实,CR能明显延缓衰老,延长实验动物的寿命,推迟和降低老年相关疾病的发生。由于世界范围内人口老龄化     

Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction

The most common manifestation of cardiovascular (CV) diseases is the presence of arterial hypertension (AH), which impacts on endothelial dysfunction. CV risk is associated with high values of systolic and diastolic blood pressure and depends on the presence of risk factors, both modifiable and not modifiable, such as overweight, obesity, physical exercise, smoking, age, family history, and gender. The main target organs affected by AH are the heart, brain, vessels, kidneys, and eye retina. AH onset can be counteracted or delayed by adopting a proper diet, characterized by a low saturated fat and sodium intake, a high fruit and vegetable intake, a moderate alcohol consumption, and achieving and maintaining over time the ideal body weight. In this review, we analyzed how a new nutritional approach, named caloric restriction diet (CRD), can provide a significant reduction in blood pressure values and an improvement of the endothelial dysfunction. In fact, CRD is able to counteract aging and delay the onset of CV and neurodegenerative diseases through the reduction of body fat mass, systolic and diastolic values, free radicals production, and oxidative stress. Currently, there are few studies on CRD effects in the long term, and it would be advisable to perform observational studies with longer follow-up.     

Effects of Caloric Restriction and Rope-Skipping Exercise on Cardiometabolic Health: A Pilot Randomized Controlled Trial in Young Adults

The aim of this study is to investigate the effects of calorie restriction (CR), rope-skipping (RS) exercise, and their joint effects on cardiometabolic health in young adults. An 8-week randomized trial was conducted on 46 undergraduates aged 19–21 y from South China. The participants were randomized into the following three groups: Calorie restriction (CR) group (n = 14), Rope-skipping (RS) group (n = 14), and CR plus RS (CR–RS) group (n = 12). At both allocation and the end of the intervention, data on anthropometry, serum metabolic, and inflammatory markers were collected. A total of 40 participants completed the intervention and were included in the analysis. After the 8-week intervention, the participants from the CR group and the CR–RS group reduced in body weight (−1.1 ± 1.7 kg, −1.3 ± 2.0 kg), body mass index (−0.4 ± 0.6 kg/m², −0.5 ± 0.7 kg/m²), body fat percentage (−1.2 ± 1.6%, −1.7 ± 1.8%), and body fat mass (−1.1 kg (−2.2, −0.3), −1.1 kg (−2.5, −0.4)) compared to the baseline (p < 0.05 or p = 0.051). For metabolic and inflammatory factors, the participants in the CR–RS group showed significant decreases in low density lipoprotein cholesterol (−0.40 mmol/L) and interleukin-8 (−0.73 mmol/L). While all the above markers showed no significant difference among the groups after intervention, in the subgroup of overweight/obese participants (n = 23), the CR–RS group had significantly lower blood pressure, fasting insulin, homeostatic model assessment of insulin resistance, tumor necrosis factor-α, and interleukin-8 levels than the CR or RS groups (p < 0.05). In conclusion, both CR and CR–RS could reduce weight and improve body composition in young adults. More importantly, in those with overweight or obesity, CR–RS intervention might be superior to either CR or RS in improving cardiometabolic health.     

The Effect of Caloric Restriction with and without n-3 PUFA Supplementation on Bone Turnover Markers in Blood of Subjects with Abdominal Obesity: A Randomized Placebo-Controlled Trial

Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25–40 kg/m²) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300–2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect.     

长期噪声暴露对大鼠海马CRF系统的影响

目的 探讨长期噪声暴露对大鼠海马组织中促肾上腺皮质激素释放激素(CRF)信号系统的影响。方法 选择Wistar雄性大鼠64只,随机分为对照组和暴露组,每组32只,暴露组暴露条件为95 dB白噪声,4 h/d×30 d,停止噪声暴露分别恢复0、3、7、14 d;对照组动物除不接受噪声暴露外,其他条件与暴露组相同。采用逆转录-聚合酶链反应(RTPCR)和免疫印迹(Western blot)法检测海马组织中促肾上腺皮质激素释放激素及其受体(CRF、CRFR1、CRFR2)的mRNA及蛋白表达水平。结果 暴露组大鼠海马CRF、CRFR1 mRNA及蛋白表达水平在停止噪声暴露后恢复0、3、7 d明显高于对照组差异有统计学意义(P0.05),到14 d时恢复到正常水平;暴露组CRFR2 mRNA及蛋白表达水平在恢复0 d无明显变化,恢复3、7 d时明显升高差异有统计学意义(P0.05),到14 d时其蛋白表达恢复到正常水平,mRNA水平依然明显高于对照组。结论 长期噪声暴露可引发大鼠海马CRF及其受体系统持续异常改变,其可能参与了噪声暴露致阿尔茨海默病症(AD)样变的进程。     

Combination of Caloric Restriction and a Mixed Training Protocol as an Effective Strategy to Counteract the Deleterious Effects in Trabecular Bone Microarchitecture Caused by a Diet-Induced Obesity in Sprague Dawley Rats

The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0–12 w, weight loss intervention 12–15 w, weight maintenance intervention 15–21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.     

Effects of Asiatic Acid on Spatial Working Memory and Cell Proliferation in the Adult Rat Hippocampus

Asiatic acid is a pentacyclic triterpene from Centella asiatica. Previous studies have reported that asiatic acid exhibits antioxidant and neuroprotective activities in cell culture. It also prevents memory deficits in animal models. The objective of this study was to investigate the relationship between spatial working memory and changes in cell proliferation within the hippocampus after administration of asiatic acid to male Spraque-Dawley rats. Control rats received vehicle (propylene glycol) while treated rats received asiatic acid (30 mg/kg) orally for 14 or 28 days. Spatial memory was determined using the novel object location (NOL) test. In animals administered asiatic acid for both 14 and 28 days, the number of Ki-67 positive cells in the subgranular zone of the dentate gyrus was significantly higher than in control animals. This was associated with a significant increase in their ability to discriminate between novel and familiar object locations in a novel object discrimination task, a hippocampus-dependent spatial memory test. Administration of asiatic acid also significantly increased doublecortin (DCX) and Notch1 protein levels in the hippocampus. These findings demonstrate that asiatic acid treatment may be a potent cognitive enhancer which improves hippocampal-dependent spatial memory, likely by increasing hippocampal neurogenesis.     

Caloric restriction and calcium's effect on bone metabolism and body composition in overweight and obese premenopausal women

Obesity results in numerous preventable deaths and comorbidities. Unfortunately, a reduction of body weight has been correlated with a reduction in bone mass, the reasons for which have not been fully elucidated. The importance of maximizing peak bone mass during premenopausal years is well known. Most studies demonstrate a positive relationship between calcium intake and bone mass. However, during caloric restriction, which is commonly used for weight loss, calcium intake has shown mixed results. Calcium from dairy sources has received additional attention, beyond its importance to bone, for its role in regulating body weight and composition. Dairy foods are perceived as high fat, and therefore, are generally minimized or avoided during caloric restriction. The current calcium intake for premenopausal women is significantly below recommendations, and even if met during caloric restriction, may not be adequate. This review underscores the need for maintaining at least adequate intake levels of calcium, if not more, during weight loss regimens to minimize potential long-term detrimental effects on bone metabolism.     

孕鼠1800MHz电磁波暴露对子代海马细胞凋亡的影响

[目的]探讨孕期暴露1800MHz电磁波对子代大鼠海马细胞凋亡的影响。[方法]以7周龄无特定病原体（SPF）级SD大鼠24只（雌鼠16只、雄鼠8只）,雌雄2：1合笼。孕鼠随机分为0．5mW／cm^2暴露组、对照1组;1．0mW／cm^2暴露组、对照2组;暴露组采用1800MHz射频电磁波对大鼠于孕第0～20天进行连续21d全身暴露,每天12h,功率密度分别为0．5mW／cm^2和1．0mW／cm^2。各组于出生后第3周和第7周时,分别随机抽取8只仔鼠（雌雄各半）测定其海马细胞凋亡率。[结果]孕期暴露于密度为1800MHz0．5mW／cm^2的电磁波,3周龄仔鼠海马细胞凋亡率显著高于两对照组和1．0mW／cm^2暴露组（P〈0．05）,1．0mW／cm^2暴露组海马细胞凋亡率与两个对照组相比,差异无统计学意义（P〉0．05）;7周龄仔鼠海马细胞凋亡率,0．5mW／cm^2和1．0mW／cm^2组均高于两个对照组（P〈0．05）,两个对照组相比差异无统计学意义（P〉0．05）。[结论]大鼠孕期暴露于1800MHz功率密度为0．5mW／cm^2和1．0mW／cm^2的电磁波可致发育期和成年期子代大鼠海马细胞凋亡率升高。     

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H₂S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H₂S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H₂S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H₂S generation, with translational implications for radiation treatment and aging.     

Temporal Dynamics of the Intestinal Microbiome Following Short-Term Dietary Restriction

Short-term dietary restriction has been proposed as an intriguing pre-operative conditioning strategy designed to attenuate the surgical stress response and improve outcomes. However, it is unclear how this nutritional intervention influences the microbiome, which is known to modulate the systemic condition. Healthy individuals were recruited to participate in a four-day, 70% protein-restricted, 30% calorie-restricted diet, and stool samples were collected at baseline, after the restricted diet, and after resuming normal food intake. Taxonomy and functional pathway analysis was performed via shotgun metagenomic sequencing, prevalence filtering, and differential abundance analysis. High prevalence species were altered by the dietary intervention but quickly returned to baseline after restarting a regular diet. Composition and functional changes after the restricted diet included the decreased relative abundance of commensal bacteria and a catabolic phenotype. Notable species changes included Faecalibacterium prausnitzii and Roseburia intestinalis, which are major butyrate producers within the colon and are characteristically decreased in many disease states. The macronutrient components of the diet might have influenced these changes. We conclude that short-term dietary restriction modulates the ecology of the gut microbiome, with this modulation being characterized by a relative dysbiosis.     

Effects on Cholesterol Balance and LDL Cholesterol in the Rat of a Soft-Ripened Cheese Containing Vegetable Oils

Objective: The purpose of this study was to examine effects of a modified soft-ripened cheese containing vegetable oils on cholesterol status, using the rat as the experimental model and the traditional soft-ripened cheese as the control.

Methods: Adult male Wistar rats (≈370 g) were divided into two dietary groups (20 rats/group) and fed either the standard diet (STD, containing traditional cheeses made from whole milk) or the experimental diet (EXP, containing modified cheeses made from the combination of skim milk with the following fat mixture: milk fat/oleic acid-enriched sunflower oil/soybean oil mixture). Lipids of the diets came solely from cheeses (14 g/100 g diet); the EXP diet contained (3-fold) less saturated fat, (2-fold) less cholesterol, and (15-fold) more phytosterols than the STD diet.

Results: Although serum triglyceride and total cholesterol concentrations were not affected by the type of diet, the EXP diet resulted in a significant reduction of LDL-cholesterol (31%, p<0.001) and a significant increase of HDL-cholesterol (11%, p<0.05), compared to the STD diet. Thus, a marked reduction (39%) of serum LDL/HDL cholesterol ratio was observed in the EXP group (p<0.001). In addition, the two quantitative balances (excreted/ingested) of cholesterol and total neutral sterols (for which phytosterols were excluded) were significantly higher by 183% and 174%, respectively for the EXP group, compared to the STD group (p<0.05). On another hand, rats fed the EXP diet excreted more cholesterol than they ingested dietary cholesterol (cholesterol balance ? 1), indicating that those animals eliminated some endogenous cholesterol in their feces, while the opposite was true for rats fed the STD diet (cholesterol balance < 1). Finally, fecal bile salt concentration was not significantly different between the two dietary groups.

Conclusions: The partial substitution of milk fat by vegetable oils in soft-ripened cheese resulted in a decreased blood LDL/HDL cholesterol ratio and an increased fecal excretion of endogenous cholesterol and neutral sterols and, thus, markedly improved its nutritional qualities. Therefore, the consumption of the described modified cheese may meet the demand of subjects who wish to lower their risk for atherosclerosis and cardiovascular disease.     

The Potential of Calorie Restriction and Calorie Restriction Mimetics in Delaying Aging: Focus on Experimental Models

Aging is a biological process determined by multiple cellular mechanisms, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication, that ultimately concur in the functional decline of the individual. The evidence that the old population is steadily increasing and will triplicate in the next 50 years, together with the fact the elderlies are more prone to develop pathologies such as cancer, diabetes, and degenerative disorders, stimulates an important effort in finding specific countermeasures. Calorie restriction (CR) has been demonstrated to modulate nutrient sensing mechanisms, inducing a better metabolic profile, enhanced stress resistance, reduced oxidative stress, and improved inflammatory response. Therefore, CR and CR-mimetics have been suggested as powerful means to slow aging and extend healthy life-span in experimental models and humans. Taking into consideration the difficulties and ethical issues in performing aging research and testing anti-aging interventions in humans, researchers initially need to work with experimental models. The present review reports the major experimental models utilized in the study of CR and CR-mimetics, highlighting their application in the laboratory routine, and their translation to human research.     

Effect of Chronic Moderate Caloric Restriction on the Reproductive Function in Aged Male Wistar Rats

Caloric restriction (CR) has been shown to be an effective nutritional intervention for increasing longevity in some animal species. The objective of this study was to evaluate CR’s effects on metabolic and reproductive parameters in 12-month-old male Wistar rats. The rats were distributed in three groups: control, CR at 15%, and CR at 35% for 6 (up to 18 months of age) and 12 months (up to 24 months of age). At the end of CR treatment, we evaluated reproductive (male sexual behavior (MSB), sperm quality) and biochemical parameters (plasma glucose, glucose-regulating hormone, and sex steroid levels), and quantified annexin V in the seminiferous epithelium. Results showed that MSB and sperm quality were improved after 6 months of CR associated with increases in plasma testosterone and decrease annexin V in the seminiferous epithelium of the testicles compared to their control group. The metabolic profile of the CR rats also improved compared to controls. However, these effects of CR on reproductive parameters were not maintained after 12 months of CR. Findings suggest that beginning CR at the age of maturity reestablishes the behavioral sexual response and reproductive function in older animals after 6 months of CR and improves endocrine functioning during aging.     

电刺激大鼠岛叶对心电图和心率变异性的影响

目的　探讨电刺激大鼠岛叶对心脏心电图、心率变异性 (heartratevariability ,HRV)的影响。方法　将 3 6只健康雄性大鼠随机分成 2组 ,对照组及岛叶刺激组 ,每组 18只 ,用 5 0 0 μA、5 0HZ电流刺激大鼠岛叶 1h后 ,观察大鼠的ECG变化 ;将 42只健康雄性大鼠随机分成 3组 ,假手术组、对照组、岛叶刺激组 ,其中对照组与岛叶刺激组又分为 70uA、5 0 0uA、15 0 0uA ,5 0HZ刺激组 ,每组 6只 ,刺激大鼠岛叶 1h后 ,观察大鼠的血压、心率、HRV参数值。结果　 5 0 0uA电流刺激后 ,岛叶刺激组的ECG发生变化 ,并且血压、心率较假手术组、对照组明显升高 ,差异有显著性 ;70uA、5 0 0uA、15 0 0uA电刺激岛叶皮质时 ,5 0 0uA、15 0 0uA刺激组的HRV的参数值降低 ,即均方根值 (squarerootofthemeansquareddifferencesofsuccessiveNNintervals ,RMSSD)、相邻心搏间期差 >10ms的间期数占RR间期总数的百分比、总频、高频、低频、混沌参数均降低 ,而低频 /高频升高 ,与 70uA刺激组及相应对照组比较 ,差异有显著性 ,提示心脏副交感神经活性降低 ,交感神经活性增强 ,且 15 0 0uA刺激组较 5 0 0uA刺激组HRV的各项指标降低更明显。结论　提示病理生理性岛叶激活如卒中、癫痫发作及一些严重应激等 ,可导致心脏的ECG、血压、心率、     

Adipose Tissue Aging and Metabolic Disorder,and the Impact of Nutritional Interventions

Adipose tissue is the largest and most active endocrine organ, involved in regulating energy balance, glucose and lipid homeostasis and immune function. Adipose tissue aging processes are associated with brown adipose tissue whitening, white adipose tissue redistribution and ectopic deposition, resulting in an increase in age-related inflammatory factors, which then trigger a variety of metabolic syndromes, including diabetes and hyperlipidemia. Metabolic syndrome, in turn, is associated with increased inflammatory factors, all-cause mortality and cognitive impairment. There is a growing interest in the role of nutritional interventions in adipose tissue aging. Nowadays, research has confirmed that nutritional interventions, involving caloric restriction and the use of vitamins, resveratrol and other active substances, are effective in managing adipose tissue aging’s adverse effects, such as obesity. In this review we summarized age-related physiological characteristics of adipose tissue, and focused on what nutritional interventions can do in improving the retrogradation and how they do this.     

The Ability of Exercise to Mitigate Caloric Restriction-Induced Bone Loss in Older Adults: A Structured Review of RCTs and Narrative Review of Exercise-Induced Changes in Bone Biomarkers

Despite the adverse metabolic and functional consequences of obesity, caloric restriction- (CR) induced weight loss is often contra-indicated in older adults with obesity due to the accompanying loss of areal bone mineral density (aBMD) and subsequent increased risk of fracture. Several studies show a positive effect of exercise on aBMD among weight-stable older adults; however, data on the ability of exercise to mitigate bone loss secondary to CR are surprisingly equivocal. The purpose of this review is to provide a focused update of the randomized controlled trial literature assessing the efficacy of exercise as a countermeasure to CR-induced bone loss among older adults. Secondarily, we present data demonstrating the occurrence of exercise-induced changes in bone biomarkers, offering insight into why exercise is not more effective than observed in mitigating CR-induced bone loss.     

Caloric Restriction Prevents Metabolic Dysfunction and the Changes in Hypothalamic Neuropeptides Associated with Obesity Independently of Dietary Fat Content in Rats

Energy restriction is a first therapy in the treatment of obesity, but the underlying biological mechanisms have not been completely clarified. We analyzed the effects of restriction of high-fat diet (HFD) on weight loss, circulating gut hormone levels and expression of hypothalamic neuropeptides. Ten-week-old male Wistar rats (n = 40) were randomly distributed into four groups: two fed ad libitum a normal diet (ND) (N group) or a HFD (H group) and two subjected to a 25% caloric restriction of ND (NR group) or HFD (HR group) for 9 weeks. A 25% restriction of HFD over 9 weeks leads to a 36% weight loss with regard to the group fed HFD ad libitum accompanied by normal values in adiposity index and food efficiency ratio (FER). This restriction also carried the normalization of NPY, AgRP and POMC hypothalamic mRNA expression, without changes in CART. Caloric restriction did not succeed in improving glucose homeostasis but reduced HFD-induced hyperinsulinemia. In conclusion, 25% restriction of HFD reduced adiposity and improved metabolism in experimental obesity, without changes in glycemia. Restriction of the HFD triggered the normalization of hypothalamic NPY, AgRP and POMC expression, as well as ghrelin and leptin levels.     

锌对睡眠剥夺小鼠大脑皮层一氧化氮合酶的影响

目的观察锌对小鼠睡眠剥夺(sleep deprivation SD)后休息不同时间大脑皮层一氧化氮合酶(Nitric oxide synthase NOS)的影响。方法用小平台水环境法建立小鼠SD模型,用NADPH-d组化法显示NOS阳性结构的存在。并计数大脑皮层的全部阳性神经元。结果SD后休息0 h组(R 0 h组)、4h组(R4 h组)与对照组(CC组)相比,NOS阳性神经元数显著升高(P<0.01),SD后休息8 h组(R 8 h组)显著下降(P<0.01),其它组差异无统计学意义。SD后休息0h补锌组(R 0 h Zn组)较R 0 h组、SD后休息4 h补锌组(R 4 h Zn组)较R 4 h组NOS阳性神经元数显著降低(P<0.01),SD后休息8 h补锌组(R 8 h Zn组)较R8h组NOS阳性神经元数显著升高(P<0.01),SD后休息12 h补锌组(R 12 h Zn组)与R 12 h组相比NOS阳性神经元数升高不明显。结论锌可对抗SD引起的NOS活力改变,促进学习记忆的恢复。     

Corticosterone and Glucocorticoid Receptor in the Cortex of Rats during Aging—The Effects of Long-Term Food Restriction

Numerous beneficial effects of food restriction on aging and age-related pathologies are well documented. It is also well-established that both short- and long-term food restriction regimens induce elevated circulating levels of glucocorticoids, stress-induced hormones produced by adrenal glands that can also exert deleterious effects on the brain. In the present study, we examined the effect of long-term food restriction on the glucocorticoid hormone/glucocorticoid receptor (GR) system in the cortex during aging, in 18- and 24-month-old rats. Corticosterone level was increased in the cortex of aged ad libitum-fed rats. Food restriction induced its further increase, accompanied with an increase in the level of 11β-hydroxysteroid dehydrogenase type 1. However, alterations in the level of GR phosphorylated at Ser²³² were not detected in animals on food restriction, in line with unaltered CDK5 level, the decrease of Hsp90, and an increase in a negative regulator of GR function, FKBP51. Moreover, our data revealed that reduced food intake prevented age-related increase in the levels of NFκB, gfap, and bax, confirming its anti-inflammatory and anti-apoptotic effects. Along with an increase in the levels of c-fos, our study provides additional evidences that food restriction affects cortical responsiveness to glucocorticoids during aging.