冬南瓜醇提物干预雄性大鼠齿状回细胞增殖和空间学习功能的变化

Previous studies reported that some plants,including butternut squash,exert positive effects on the brain.However,few studies have examined the effects of butternut squash on learning,memory,and neurogenesis.This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats.Thirty-five male Wistar rats were intrap-eritoneally injected with 0,50,100,200 and 400 mg/kg butternut squash extract once daily for 2 months.After the last administration,rat’s spatial memory was studied using the Morris water maze.Finally,rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies.The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats,and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls.These findings suggest that butternut squash extract improves the learning and memory abilities of male rats,and increases the proliferation of dentate gyrus cells.     

一氧化氮对应激新生大鼠前额皮质的保护

Nitric oxide (NO) has been shown to have both protective and detrimental effects in central nervous system (CNS). This survey aims to demonstrate the effect of NO on the prefrontal cortex in neonatal stressed rats. Materials and Methods: Forty-eight male Wistar rats (80-100gr) divided randomly in two groups: stressed and non-stressed, then each group divided equally into four subgroups. The stress was induced by immobilizing of the animals every other day, for 4 weeks. Each rat received only one of these materials: saline, L-Arginine (200 mg/kg IP) as a nitric oxide synthase (NOS) inducer, L-Name (2O mg/kg IP) or 7- nitroindazole (25 mg/kg S.C), for 4 weeks. After that the brain was removed and divided in two parts by a coronal section. Anterior and posterior part was used for histological studies and the measure of nitric oxide, respectively. Results: There was a significant decrease in NO production with less thickness of prefrontal cortex in stressed rats especially in rats which received 7- nitroindazole and L-Name compare to the group that received L-Arginine. Conclusion: L-Arginine has a protective effect on the cortex in neonatal stressed rats while 7-nitroindazole and L-Name lead to increase damage in non-stressed groups.     

A comparative study of Lrrk2 function in primary neuronal cultures

ObjectiveTo assess the contribution of wild-type, mutant and loss of leucine-rich repeat kinase-2 (LRRK2; Lrrk2) on dendritic neuronal arborization.BackgroundLRRK2 mutations are recognized as the major genetic determinant of susceptibility to Parkinson’s disease for which a cellular assay of Lrrk2 mutant function would facilitate the development of targeted molecular therapeutics.MethodsDendritic neuronal arborization (neurite length, branching and the number of processes per cell) was quantified in primary hippocampal and midbrain cultures derived from five lines of recombinant LRRK2 mice, including human BAC wild-type and mutant overexpressors (Y1699C and G2019S), murine knock-out and G2019S knock-in animals.ResultsNeuronal arborization in cultures from BAC Lrrk2 wild-type animals is comparable to non-transgenic littermate controls, despite high levels of human transgene expression. In contrast, primary neurons from both BAC mutant overexpressors presented with significantly reduced neuritic outgrowth and branching, although the total number of processes per cell remained comparable. The mutant-specific toxic gain-of-function observed in cultures from BAC mutant mice may be partially rescued by staurosporine treatment, a non-specific kinase inhibitor. In contrast, neuronal arborization is far more extensive in neuronal cultures derived from murine knock-out mice that lack endogenous Lrrk2 expression. In Lrrk2 G2019S knock-in mice, arguably the most physiologically relevant system, neuritic arborization is not impaired.ConclusionsImpairment of neuritic arborization is an exaggerated, albeit mutant specific, consequence of Lrrk2 over-expression in primary cultures. The phenotype and assay described provides a means to develop therapeutic agents that modulate the toxic gain-of-function conferred by mutant Lrrk2.     

LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease

Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of LINGO1 and its paralog LINGO2 in ET and PD by sequencing both genes in patients (ET, n?=?95; PD, n?=?96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET, n?=?1,247; PD, n?=?633) and controls (n?=?642). The sequencing study identified six novel coding variants in LINGO1 (p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in LINGO2 (p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. The association study employed 16 tSNPs at the LINGO1 locus and 21 at the LINGO2 locus. One variant in LINGO1 (rs9652490) displayed evidence of an association with ET (odds ratio (OR)?=?0.63; P?=?0.026) and PD (OR?=?0.54; P?=?0.016). Additionally, four other tSNPs in LINGO1 and one in LINGO2 were associated with ET and one tSNP in LINGO2 associated with PD (P?<?0.05). Further analysis identified one tSNP in LINGO1 and two in LINGO2 which influenced age at onset of ET and two tSNPs in LINGO1 which altered age at onset of PD (P?<?0.05). Our results support a role for LINGO1 and LINGO2 in determining risk for and perhaps age at onset of ET and PD. Further studies are warranted to confirm these findings and to determine the pathogenic mechanisms involved.     

Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease

Mitochondrial dysfunction has been proposed to play a role in the pathogenesis of Parkinson's disease (PD). Supportive of this hypothesis, several genetic variants that regulate mitochondrial function and homeostasis have been described to alter PD susceptibility. A recent report demonstrated association of a single nucleotide polymorphism in the mitochondrial translation initiation factor 3 (MTIF3) gene with PD risk. The protein encoded by this nuclear gene is essential for initiation complex formation on the mitochondrial 55S ribosome and regulates translation of proteins within the mitochondria. Changes in the function or expression of the MTIF3 protein may result in altered mitochondrial function, ATP production or formation of reactive oxygen species thereby affecting susceptibility to PD. We examined the association of rs7669 with sporadic PD in three Caucasian case control series (n=2434). A significant association was observed in the largest series (Norwegian; n=1650) when comparing CC vs. CT/TT genotypes, with the Irish and US series having a similar but non-significant trend. The combined series also revealed an association with risk of PD (P=0.01), supporting the possible involvement of this gene in PD etiology.     

Low serum leptin serves as a biomarker of malnutrition in elderly patients

Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P < .001) compared with the malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P < .001), but no significant correlation with C-reactive protein. Sex, weight, and triglyceride were the best predictors of serum leptin (all P < .001). The optimal cutoff value of serum leptin to detect malnutrition was 4.3 ng/mL in men and 25.7 ng/mL in women. Serum leptin may be a good predictor of nutritional status in elderly patients.     

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a,and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100?mg CC or 5?mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.     

Objective assessment of obstructive sleep apnea in normal pregnant and preeclamptic women

Objective: Obstructive sleep apnea (OSA) is a risk factor for adverse pregnancy outcomes. The aim of this study was to evaluate the association between OSA and preeclampsia. Methods: Between 30 and 39 weeks gestation, objective sleep apnea were evaluated in 38 normal pregnant and 40 preeclamptic women. Preeclampsia was defined by having a blood pressure (BP) > 140/90 mmHg on two occasions after the 20th week of pregnancy with excess protein in the urine (> 300 mg in 24 h) or 30 mg persistent proteinuria (+ 1 in dipsticks) in random samples. Objective sleep apnea was evaluated using an overnight in-hospital sleep evaluation using the SOMNOwatch plus Respiratory Screener. OSA was defined as an apnea–hypopnea index (AHI) ≥ 5, and further grouped into severity categories: mild (5–14.9), moderate (15–29.9), and severe (≥ 30). Results: Mean AHI was 33.3 ± 12.1 in preeclamptic women and was 23.8 ± 15.8 in normal pregnant women (p = 0.008). There was significant difference in prevalence of OSA severity (none, mild, moderate, or severe) between groups. Out of 33 preeclamptic women, 11 women had moderate and 22 women had severe OSA. Whereas, among 33 normal pregnant women, 8, 13, and10 women had mild, moderate, and severe OSA, respectively. Two normal pregnant women had no OSA (AHI< 5). Conclusion: Our study suggests women are susceptible to developing OSA during pregnancy that is associated with an increased risk of preeclampsia.