Effects of a Cardiotonic Medicine,Danshen Pills,on Cognitive Ability and Expression of PSD-95 in a Vascular Dementia Rat Model

A widely used Chinese cardiotonic proprietary medicine, compound Danshen dripping pills (CDDP, Fufang Danshen Diwan) has also begun to be used for treatment of vascular dementia (VaD). We tried to explore the mechanism of CDDP action in this case. A VaD experimental model was built in rats by bilateral ligation of the common carotid arteries. The cognitive ability of experimental animals was evaluated in the Morris water maze test. Synaptic ultrastructural changes in the hippocampus were detected by transmission electron microscopy; expression of PSD-95 mRNA in the hippocampus was examined using hybridization in situ. The latter index (mRNA expression) in the VaD group was significantly lower than those in the CDDP and sham-operated groups (P < 0.05). CDDP treatment considerably improved disturbed ultrastructural synaptic characteristics in the hippocampus of VaD rats. The mean escape latency in the Morris water maze test was significantly shorter in CDDP-treated VaD rats, compared with that those of the VaD group (P < 0.05). In the CDDP group compared to the VaD one, escape strategies improved from edge and random searches to more linear swim pathway (P < 0.05). Thus, decreasing expression of PSD-95 plays an important role in the pathogenesis of VaD. CDDP treatment improves the learning and memory ability of VaD rats by improving neural synaptic ultrastructural characteristics and increasing expression of PSD-95 mRNA in the hippocampus.     

Study on Blood Biochemical Diagnostic Indices for Hepatic Function Biomarkers in Endemic Skeletal Fluorosis

The aim of the study was to determine the relationship of fluoride in drinking water to liver function in individuals living in normal and seven endemic fluorosis areas of Punjab, India. The concentration of fluoride in drinking water of different areas varied from 5.9 to 24.5 mg/L. Study group consisted of 705 patients in the age group between 20 and 60 years (mean age of 39.35 ± 11.27) affected with osteodental fluorosis were compared with 300 age- and sex-matched controls (with mean age of 35.28 ± 8.25 years). Biochemical data was analyzed by one-way analysis of variance (ANOVA) with post hoc Tukey–Kramer and Bonferroni multiple comparison tests. The relationship between hepatic enzymes was calculated by Pearson’s correlation and linear regression. The results revealed significantly (P < 0.001) higher concentration of serum fluoride in patients when compared to control. The mean activities of cyclic adenosine monophosphate (AMP), alkaline phosphatase (ALKP), acid phosphatase (ACP), aspartate aminotransaminase (AST), and alanine aminotransaminase (ALT) were significantly (P < 0.05–0.001) elevated in patients from all fluoride areas. ANOVA with post hoc Turkey–Kramer and Bonferroni multiple comparison test demonstrated a significant (P < 0.0001) variance in the activities of cAMP, ALKP, ACP, AST, and ALT in fluorotic patients, with elevation in water fluoride levels. Maximum elevation of 196.14% (ACP), 99.31% (cyclic adenosine monophosphate; cAMP), 72.08% (ALT), 60.14% (AST), and least 21.35% (ALKP) was recorded in patients exposed to 24.5 mg/L fluoride in drinking water. There was positive correlation between water fluoride, serum fluoride and AST (r = 0.77, 0.91), ALT (r = 0.82, 0.90), ALKP (r = 0.88, 0.97), and ACP (r = 0.74, 0.85). Pearson’s correlation demonstrated highly significant (P < 0.05) positive relationship between water fluoride and cAMP (regression equation: Y = 0.9807 ×+ 22.081 Y = 0.9807 \times + 22.081 , = 0.84; r = 0.92, P < 0.05). The increased levels of transaminases in fluorotic patients suggest alteration in liver functions. The level of alkaline and acid phosphatase was increased during fluoride intoxication which is also an early marker of hepatic cell damage because of its specificity and catalytic activity. The elevated levels of enzymes are reflective of bone disorders, which are characterized by increased osteoblastic activity. There levels increased several times if cellular damage occurs in the liver. The results suggest that fluoride exposure intensifies the activities of hepatic function enzymes in osteofluorosis.     

Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain

It has been shown that induction of HSP70 by administration of geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion injury. The present study was performed to determine the effect of GGA on the survival of mice and on brain damage under acute hypobaric hypoxia. The data showed that the mice injected with GGA survived significantly longer than control animals (survival time of 9.55 ± 3.12 min, n = 16 vs. controls at 4.28 ± 4.29 min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of the hippocampus and the cortex induced by sublethal hypoxia for 6 h could be attenuated by preinjection with GGA, especially in the CA2 and CA3 regions of the hippocampus. In addition, the activity of nitric oxide synthase (NOS) of the hippocampus and the cortex was increased after exposure to sublethal hypoxia for 6 h but could be inhibited by the preinjection of GGA. Furthermore, the expression of HSP70 was significantly increased at 1 h after GGA injection. These results suggest that administration of GGA improved survival rate and prevented acute hypoxic damage to the brain and that the underlying mechanism involved induction of HSP70 and inhibition of NOS activity.     

Brain acetylcholinesterase activity of the American pronghorn antelope <Emphasis Type="Italic">(Antilocapra americana)</Emphasis> collected from the US Army Dugway Proving Ground,Utah

Brain tissue was analyzed for acetylcholinesterase (AChE) activity from 24 American pronghorn antelope (Antilocapra americana) collected on the US Army Dugway Proving Ground (DPG) (latitude 40°13' 52" N, longitude 112°45' 01" W), Tooele County, Utah. Pronghorn antelope from DPG were evaluated against 26 pronghorn antelope collected in Wyoming. The mean AChE activity was significantly greater (P < 0.001) in the Wyoming control group (4.612 ± 0.193 μM/gm brain tissue/min) relative to DPG (4.032 ± 0.621 μM/gm brain tissue/min). The DPG database exhibited a fourfold greater coefficient of variation, a tenfold greater variance, and a threefold increase in the standard deviation when compared to control AChE activity. Furthermore, the 95% confidence interval for the control and for the DPG data were not overlapping; the entire control data set was greater than the mean DPG AChE activity. A post hoc sequential Bonferroni statistical procedure showed two significantly (P < 0.001) distinct subsets in the DPG data. Mean DPG Subset I AChE activity (4.528 ± 0.347 μM/gm brain tissue/min) was indistinct from the mean control AChE value (4.612 ± 0.193 μM/gm brain tissue/min). The mean DPG Subset II AChE activity (3.537 ± 0.387 μM/gm brain tissue/min) differed significantly (P < 0.001) from the mean control AChE activity. The sum of resulting α values from the multiple statistical tests did not exceed the selected α value of P < 0.05, validating the post hoc sequential Bonferroni statistical procedure. Pronghorn antelope represented by Subset II, experienced a 23.3% mean loss of AChE activity suggesting sub-lethal organophosphate (OP) exposure rather than a low level chronic environmental influence was experienced by a population subset of the DPG pronghorn antelope herd. The origin of the DPG sublethal OP exposure and its long-term effects are speculative.     

Effect of Different Selenium Sources on Productive Performance,Serum and Milk Se Concentrations,and Antioxidant Status of Sows

The experiment was conducted to study the effects of different selenium (Se) sources on productive performance, serum and milk Se concentrations, and antioxidant status of sows. A total of 12 sows (Landrace×Yorkshire) with same pregnancy were randomly divided into two groups; each group was replicated six times. These two groups received the same basal gestation and lactation diets containing 0.042 mg Se/kg, supplemented with 0.3 mg Se/kg sodium selenite or selenomethionine (i.e., seneno-dl-methylseleno), respectively. The feeding trial lasted for 60 days, with 32 and 28 days for gestation and lactation period, respectively. Compared with sodium selenite, maternal selenomethionine intake significantly increased (P < 0.05) the weaning litter weight and average weight of piglet. The Se concentration in the serum, colostrum, and milk of sows were significantly higher (p < 0.05) in the selenomethionine-treated group. The antioxidant status was greatly improved in sows of selenomethionine-treated group and was illuminated by the increased total antioxidant capability (T-AOC; P < 0.05) and decreased malondialdehyde (MDA; P < 0.01) level in the serum of sows, increased T-AOC (P < 0.05), glutathione (GSH) peroxidase (P < 0.05), superoxide dismutase (P < 0.05) and GSH (P < 0.05), and MDA (P < 0.05) level in the colostrum and milk of sows. These results suggested that maternal selenomethionine intake improved Se concentration and antioxidant status of sows, thus maintain maternal health and increase productive performance after Se was transferred to its offspring.     

Alterations in Electrocardiographic Parameters after Subacute Exposure of Fluoride and Ameliorative Action of Aluminium Sulphate in Goats

Fluorosis or crippling disease is one of the existing environmental challenges for animal and human beings in most parts of the globe. In the present study, sodium fluoride alone and with aluminium sulphate (ameliorative agent) was administered orally daily for 30 days in healthy goats of group 1 and 2, respectively, to access the effect on the electrocardiogram. All waves of Lead I, Lead II, Lead III, aVR, aVL and aVF in electrocardiographs were recorded before and after 30 days exposure of fluoride. A significant (P < 0.05) increase in P–R, Q–T and S–T intervals were observed in goats of group 1 as compared to their pre treatment values. The T wave duration was also significantly (P < 0.05) prolonged and as a result, bradycardia was observed after subacute exposure of fluoride for 30 days in group 1. But, in group 2, no such changes were observed. On the basis of results, it may be concluded that subacute toxicity of fluoride produces significant changes in different waves of electrocardiogram and aluminium sulphate has ameliorative efficacy.     

Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.     

Influence of Selenium on Body Weights and Immune Organ Indexes in Ducklings Intoxicated with Aflatoxin B<Subscript>1</Subscript>

To investigate the influence of selenium on body weights and the immune organ indexes in ducklings administrated with aflatoxin B₁ (AFB₁), 90 7-day-old ducklings were randomly divided into three groups (groups I–III). Group I was used as a blank control. Group II was administered with AFB₁ (0.1 mg/kg body weight). Group III was administered with AFB₁ (0.1 mg/kg body weight) plus sodium selenite (1 mg/kg body weight). All treatments were given once daily for 21 days. It showed that the ducklings’ bursa of fabricius, thymus indexes, and body weights in group II significantly decreased when compared with group I (P < 0.01). Furthermore, the spleen indexes significantly decreased (P < 0.01). However, the ducklings’ bursa of fabricius and thymus indexes, body weights in group III ducklings significantly increased when compared with group II (P < 0.01). In addition, the spleen indexes significantly decreased (P < 0.01). These results revealed that AFB₁ significantly affect ducklings’ growth and immune organs development. However, selenium significantly ameliorated the negative effects induced by AFB₁.     

Dietary Zinc Glycine Chelate on Growth Performance,Tissue Mineral Concentrations,and Serum Enzyme Activity in Weanling Piglets

One hundred twenty crossbred piglets (Duroc × Landrace × Yorkshire) were used to determine the effects of dietary zinc glycine chelate on growth performance, tissue mineral concentrations, and serum enzyme activity. All pigs were allotted to four treatments and fed with basal diets supplemented with 0, 50, and 100 mg/kg Zn as zinc glycine chelate or 3,000 mg/kg Zn as zinc oxide (ZnO). After the 35-day feeding trial, results of the study showed that, compared to the control, average daily gain was improved (P < 0.05) for pigs fed 100 mg/kg Zn from zinc glycine chelate or 3,000 mg/kg Zn from ZnO and Zn concentrations in serum and M. longissimus dorsi were significantly enhanced by 100 mg/kg dietary zinc glycine chelate and 3,000 mg/kg ZnO. In addition, supplementation of 100 mg/kg zinc glycine chelate decreased (P < 0.05) the liver Fe level, liver Zn level, spleen Cu level, and kidney Cu level compared to that of the 3,000-mg/kg ZnO group. For feces mineral excretion, 3,000 mg/kg Zn from ZnO greatly increased the concentration of fecal Zn (P < 0.01) and Mn (P < 0.05) compared to that of the control or the 100-mg/kg zinc glycine chelate group. Moreover, alkaline phosphatase and Cu/Zn superoxide dismutase activities of pigs in 100 mg/kg zinc glycine chelate and ZnO treatments were greatly higher than that of the control. The results of present study showed that supplementation with zinc glycine chelate could improve growth and serum enzyme activities and could also decrease zinc excretion in feces in weanling pig compared to high dietary ZnO.     

Serum Parathyroid Hormone Levels in Chronic Endemic Fluorosis

Endemic waterborne fluorosis is a public health problem in Isparta, a city located in southern Turkey. Fluoride is a cumulative element that increases metabolic turnover of the bone and also affects the homeostasis of bone mineral metabolism. There are number of similarities between the effects of excess parathyroid hormone (PTH) and fluorosis on bone. So fluoride might show its effect via PTH. We aimed to determine PTH levels in patients with endemic fluorosis to estimate the possible toxic effects of chronic fluoride intake. Fifty-six patients with endemic fluorosis and 28 age-, sex-, and body-mass-index-matched healthy controls were included in this study. Endemic fluorosis was diagnosed according to the clinical diagnosis criteria of Wang. The urine fluoride levels of fluorosis patients were significantly higher than those of control subjects as expected (1.9 ± 0.1 vs. 0.4 ± 0.1 mg/L, respectively; P < 0.001). PTH levels in fluorosis group were significantly higher than control group (65.09 ± 32.91 versus 47.40 ± 20.37, respectively; P = 0.01). The results of our study demonstrate that serum PTH levels are increased in patients with endemic fluorosis. Fluoride, by interfering calcium balance, may be the cause of secondary hyperparathyroidism.     

Protection of Selenium on Hepatic Mitochondrial Respiratory Control Ratio and Respiratory Chain Complex Activities in Ducklings Intoxicated with Aflatoxin B<Subscript>1</Subscript>

To investigate the protection of selenium on hepatic mitochondrial functions, 90 7-day-old ducklings were randomly divided into three groups (groups I–III). Group I was used as a blank control. Group II was administered with aflatoxin B₁ (0.1 mg/kg body weight). Group III was administered with aflatoxin B₁ (0.1 mg/kg body weight) plus selenium (sodium selenite, 1 mg/kg body weight). All treatments were given once daily for 21 days. The results showed that the activities of hepatic mitochondrial complexes I–IV in group II ducklings significantly decreased when compared with group I (P < 0.01). Furthermore, the activities of hepatic mitochondrial complexes I–IV in group III significantly increased when compared with group II (P < 0.05). The hepatic mitochondrial respiratory control ratio (RCR) in group II ducklings significantly decreased when compared with group I (P < 0.01). In addition, the hepatic mitochondrial RCR in group III significantly increased when compared with group II (P < 0.05). These results revealed that the aflatoxin B₁ significantly induced hepatic mitochondrial dysfunction in the activities of hepatic mitochondrial respiratory chain complexes I–IV and the RCR in ducklings. However, sodium selenite could significantly ameliorate the negative effect induced by aflatoxin B₁.     

Regulation of adiponectin gene expression in adipose tissue by thyroid hormones

Available experimental data suggest that adiponectin and thyroid hormones have biological interaction in vivo. However, the effects of thyroid hormones on adipose adiponectin gene expression in thyroid dysfunction are unclear. We induced hyper- (HYPER) and hypothyroidism (HYPO) by daily administration of a 12 mg/l of levothyroxine and 250 mg/l of methimazole in drinking water of rats, respectively, for 42 days. The white adipose tissues and serum sample were taken on days 15, 28, 42 and also 2 weeks after treatment cessation. Analysis of adiponectin gene expression was performed by real-time PCR and 2^−ΔΔct method. The levels of adipose tissue adiponectin mRNA in the HYPO rats were decreased during the 6-week treatment when compared to control rats (<0.05) and were increased significantly 2 weeks after HYPO cessation (P < 0.05). This decline in adiponectin gene expression occurred in parallel with a decrease in T3, T4, fT3 and fT4 concentrations (P < 0.05). In opposite to HYPO rats, adipose adiponectin gene expression was increased in HYPER rats during the 6-week treatment in parallel with an increase the thyroid hormones concentrations (P < 0.05), and its expression was decreased 2 weeks after HYPER cessation (P < 0.05). Adiponectin gene expression levels showed significant negative correlations with concentrations of LDL (HYPO; r = −0.806, P = 0.001 and HYPER; r = −0.749, P = 0.002), triglyceride (HYPO; r = −0.825, P = 0.001 and HYPER; r = −0.824, P = 0.001) and significant positive correlations with concentrations of glucose (HYPO; r = 0.674, P = 0.004 and HYPER; r = 0.866, P = 0.001) and HDL (HYPO; r = 0.755, P = 0.001 and HYPER; r = 0.839, P = 0.001). The current study provides evidence that adiponectin gene expression in adipose tissue is regulated by thyroid hormones at the translation level and that lipid and carbohydrate disturbances in a patient with thyroid dysfunction may be, in part, due to adiponectin gene expression changes.     

Oleic acid decreases the expression of a cholesterol transport-related protein (NPC1L1) by the induction of endoplasmic reticulum stress in CaCo-2 cells

The reported data indicate that oleic acid (OA) decreases cholesterol absorption. To explore the underlying mechanisms, the effects of OA on the expression of cholesterol transport-related proteins (NPC1L1, ABCG5/8, ACAT2, MTP) and the unfolded protein response (UPR) pathway were studied in CaCo-2 enterocytes by incubating CaCo-2 cells with taurocholate micelles or taurocholate micelles containing different concentrations of OA (0.25–1.0 mM). We show that OA effectively induces XBP1 mRNA splicing, a key component of the UPR signaling, and the expression of BiP and mature ATF6 proteins in a concentration-dependent manner, leading to the induction of endoplasmic reticulum (ER) stress and activation of the UPR. Interestingly, OA decreases NPC1L1 expression in a dose-dependent manner while it has no effects on ABCG5 and MTP mRNA level or SREBP-2, ABCG8, and ACAT2 protein level. In CaCo-2 cells treated with 1.0 mM OA, both the NPC1L1 mRNA level and the NPC1L1 protein expression in brush-border membrane fractions were decreased by 39% and 37%, respectively (P < 0.01). A dose of 1 mM dithiothreitol (DTT), a positive control for ER stress induction, also decreases NPC1L1 mRNA and protein expression by 27% and 23%, respectively (P < 0.05). Furthermore, 4-phenyl-butyric acid, an UPR inhibitor, blocks OA- and DTT-induced reduction on NPC1L1 mRNA and protein levels. The results suggest that OA down-regulates NPC1L1 mRNA and protein expression via the induction of the UPR, which may play an important role in reducing intestinal cholesterol absorption.     

Serum Copper,Zinc, and Magnesium Levels in Patients with Chronic Fluorosis

Although there are many studies on effect of fluoride on trace elements in experimental animals, few studies exist on serum trace elements levels in patients with endemic fluorosis. We aimed to determine the serum levels of trace elements including serum copper (Cu), zinc (Zn), and serum levels of minerals including calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K) in patients with endemic fluorosis. The study group consisted of 30 patients with endemic fluorosis (17 females, 13 males, mean age 33.53 ± 9.85 years). An age, gender, and body mass index matched 30 healthy volunteers comprised control group (21 females, ten males with a mean age 33.93 ± 7.39 years). Urine fluoride levels of chronic fluorosis patients were significantly higher than that of control subjects as expected (1.92 ± 0.10 mg/l vs. 0.41 ± 0.09 mg/l, respectively; P < 0.001). Serum Cu levels (89.14 ± 16.77 μg/dL vs. 102.69 ± 25.04 μg/dL, respectively, P = 0.017), serum Zn levels (77.98 ± 20.58 μg/dL vs. 94.57 ± 35.87μg/dL, respectively, P = 0.032), and serum Mg levels (1.92 ± 0.18 mg/dL vs. 2.07 ± 0.31 mg/dL, respectively, p = 0.022) was significantly lower in chronic fluorosis patients than in controls. There were no statistically significant differences between the fluorosis group and control group with respect to serum levels of Na, K, Ca, and P. We concluded that chronic fluorosis is associated with reduced serum levels of Cu, Zn, and Mg.     

Zinc,Parity, Infection,and Severe Anemia Among Pregnant Women in Kassla,Eastern Sudan

The study was conducted to investigate determinants (clinical, nutritional, and nonnutritional factors) of anemia among pregnant women in Kassala, eastern Sudan. Sociodemographic characteristics were gathered; serum ferritin, zinc, albumin, and C-reactive protein were measured using different laboratory methods in a cross-sectional study of 250 pregnant women. Of the 250 women, 58.4% had anemia (hemoglobin (HB) <11 g/dl), 6.8% had severe anemia (HB < 7 g/dl), 19.6% had iron deficiency (S-ferritin <15 μg/l), 14.8% had iron deficiency anemia (<11 g/dl and S-ferritin <15 μg/l), and 38% had zinc deficiency (<80 μg/ml). S-albumin, zinc, and ferritin were significantly lower in patients with severe anemia. While age, gestational age, ferritin, and C-reactive protein were not predictors for anemia, primigravidae (OR = 2.7, 95% CI = 1.1–6.7, P = 0.02), low S-albumin (OR = 5.9, 95% CI = 1.4–25.2, P = 0.01), and low S-zinc (OR = 2.6, 95% CI = 1.0–6.6, P = 0.03) were the predictors for anemia. While there was no significant correlation between hemoglobin, S-zinc, and S-ferritin, there was a significant positive correlation between hemoglobin and S-albumin (r = 0.308, P = 0.001) and significant inverse correlation between hemoglobin and C-reactive protein (r = 0.169, P = 0.007). Thus, the role of chronic inflammation and zinc as possible contributing factors to anemia in pregnancy has important implications for the clinical evaluation and treatment of these women.     

Chronic Unpredictable Stress Before Pregnancy Reduce the Expression of Brain-Derived Neurotrophic Factor and N-Methyl-D-Aspartate Receptor in Hippocampus of Offspring Rats Associated with Impairment of Memory

To investigate the effect of stress before pregnancy on memory function and serum corticosterone (COR) levels, as well as the expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) 2A (NR2A) and 2B (NR2B) receptors in the hippocampus of the offspring rats when they were 2 months postnatally. Adult female Sprague-Dawley (SD) rats were divided randomly into two groups: control group (n = 8) and chronic unpredictable stress (CUS) group (n = 12). All rats were tested in the open field test and sucrose intake test before and after CUS. The memory function of their offspring were tested in the Morris water maze. Serum COR levels were determined by using a standard radioimmunoassay kit. The expression of BDNF, NR2A and NR2B in the hippocampus of the offspring rats were studied by immunoreactivity quantitative analysis and real-time RT-PCR. (1) Following CUS, reduced open field test activity and decreased sucrose consumption were observed relative to controls. (2) The Morris water maze task demonstrated increased escape latency in the offspring rats of CUS group relative to controls (P < 0.01). No-platform probe testing showed reduced crossings for offspring of CUS relative to controls (P < 0.05). (3) CUS induced a significant increase in serum COR levels of the offspring rats (P < 0.01), but no difference was observed in the body or brain weight between the offspring of the two groups. (4) Immunoreactivity quantitative analysis shows that BDNF and NR2B in the offspring of CUS group was decreased in the CA3 and DG regions of the hippocampus compared to the control group offspring, but NR2A levels were not altered between the offspring of the two groups. (5) Real-time RT-PCR demonstrated that BDNF and NR2B mRNAs were significantly decreased in the offspring of the CUS group compared with the control group (P < 0.01). No significant difference in the levels of NR2A mRNA was detected between offspring of CUS and offspring of control groups. In our study, pregestational stress can increase serum corticosterone levels and reduce the expression of BDNF and NR2B in the hippocampus of offspring. These alterations are associated with impairment of memory in the adult offspring. These data suggest that, stress before pregnancy might have a profound influence on brain development of offspring, that may persist into and be manifested in adulthood.     

The protective role of 5-hydroxymethyl-2-furfural (5-HMF) against acute hypobaric hypoxia

Our previous study showed that pretreatment with 5-hydroxymethyl-2-furfural (5-HMF) led to protection against hypoxic injury via a p-ERK-mediated pathway in vitro. Whether the protection of 5-HMF against hypoxia is effective in vivo is unknown. The present study is aimed to verify the role of 5-HMF in acute hypobaric hypoxia using Kunming mice as an in vivo model and further investigate the underlying mechanisms. Mice pretreated with or without 5-HMF for 1 h were exposed to acute hypobaric hypoxic condition for 6 h and then the survival time, the survival rate, the permeability of blood–brain barrier (BBB), the histological analysis in hippocampus and cortex, and the phosphorylation level of mitogen-activated protein kinases (ERK, JNK, and p38) were investigated. The results showed that 5-HMF significantly increased the survival time and the survival rate of mice. Accordingly, pretreatment with 5-HMF markedly attenuated acute hypobaric hypoxia-induced permeability of BBB (P < 0.01). In addition, the cellular damage extent of the hippocampus and the cortex induced by hypoxia for 6 h was also attenuated by pretreatment with 5-HMF, especially in the hippocampus CA1 region. Furthermore, the activation of ERK rather than JNK and p38 was involved in the protection of 5-HMF against acute hypobaric hypoxia. In summary, 5-HMF enhanced the survival capability of mice and decreased acute hypoxic damage to the brain, which may be associated with the effects on BBB and p-ERK.     

Upregulation of BACE1 and β-Amyloid Protein Mediated by Chronic Cerebral Hypoperfusion Contributes to Cognitive Impairment and Pathogenesis of Alzheimer’s Disease

Chronic cerebral hypoperfusion (CCH) increases the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between CCH and the development of AD remains uncertain. To investigate expression of APP, BACE1 and Aβ in the hippocampus of BCCAO rats and study pathophysiological mechanism of AD from CCH. CCH rat model was established by chronic bilateral common carotid artery occlusion (BCCAO). Behavior was evaluated after BCCAO with Morris water maze and open-field task. Expression of Aβ was measured by enzyme linked immunosorbent assay (ELISA). β-Amyloid precursor protein cleavage enzyme 1 (BACE1) and β-amyloid precursor protein (APP) were tested by ELISA, Western blotting and RT-PCR. Cognitive impairment occurred with CCH by Morris water maze test and open-field task. The BACE1 and Aβ level in BCCAO rats was more increased than sham-operation control rats (P < 0.01) but APP had no difference(P > 0.05). The expression of BACE1 and Aβ has no inter-grouop difference in BCCAO rats (P > 0.05). The level of BACE1 and Aβ had positive correlation with cognitive impairment (P < 0.01) while no correlation was observed between APP and cognitive impairment. Chronic cerebral ischemia contributes to cognitive impairment and vascular pathogenesis of Alzheimer’s disease that chronic cerebral hypoperfusion increases BACE1 and Aβ level in brain.     

Chromium Supplementation Can Alleviate the Negative Effects of Heat Stress on Growth Performance,Carcass Traits,and Meat Lipid Oxidation of Broiler Chicks without Any Adverse Impacts on Blood Constituents

This study was conducted to determine the effects of dietary supplementation with Cr nicotinate and Cr chloride and their optimum inclusion rate on performance, carcass traits, meat oxidative stability, serum metabolites, hematological parameters, and liver chromium concentration in heat-stressed broilers. A total number of 420, 1-day-old male broiler chicks were randomly assigned to seven treatments with four replicates of 15 chicks. The dietary treatments consisted of the basal diet supplemented with 0 (control), 500, 1,000, and 1,500 μg/kg Cr in the form of Cr nicotinate and Cr chloride. Chicks were raised for 6 weeks in heat stress condition (33 ± 2°C). Supplements of organic and inorganic Cr particularly at 1,500 μg/kg incorporation increased feed consumption (P < 0.05) and body mass gain of broilers (P < 0.01). Cr supplementation increased carcass yield and decreased abdominal fat (P < 0.01). Supplementation of 1,500 μg/kg Cr nicotinate (P < 0.05) enhanced liver Cr concentration. Storage time increased lipid oxidation of meat (P < 0.01). Cr decreased lipid oxidation of breast and thigh muscles over 2 (P < 0.01) or 6 (P < 0.05) days of storage time. Birds fed 1,500 μg/kg Cr nicotinate, had lower concentration of serum glucose and triglyceride at 21 days (P < 0.05). Hematological parameters tested at 21 and 42 days, were not influenced. The results suggested that dietary Cr supplementation regardless of its source have a positive effect on productive, and carcass traits, also enhances oxidative stability of refrigerated meat in broilers reared under heat stress conditions.