Lu Zhang

Brain-Derived Neurotrophic Factor Ameliorates Learning Deficits in a Rat Model of Alzheimer's Disease Induced by Aβ1-42

An emerging body of data suggests that the early onset of Alzheimer’s disease (AD) is associated with decreased brain-derived neurotrophic factor (BDNF). Because BDNF plays a critical role in the regulation of high-frequency synaptic transmission and long-term potentiation in the hippocampus, the up-regulation of BDNF may rescue cognitive impairments and learning deficits in AD. In the present study, we investigated the effects of hippocampal BDNF in a rat model of AD produced by a ventricle injection of amyloid-β1-42 (Aβ1-42). We found that a ventricle injection of Aβ1-42 caused learning deficits in rats subjected to the Morris water maze and decreased BDNF expression in the hippocampus. Chronic intra-hippocampal BDNF administration rescued learning deficits in the water maze, whereas infusions of NGF and NT-3 did not influence the behavioral performance of rats injected with Aβ1-42. Furthermore, the BDNF-related improvement in learning was ERK-dependent because the inhibition of ERK, but not JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected with Aβ1-42. Together, our data suggest that the up-regulation of BDNF in the hippocampus via activation of the ERK signaling pathway can ameliorate Aβ1-42-induced learning deficits, thus identifying a novel pathway through which BDNF protects against AD-related cognitive impairments. The results of this research may shed light on a feasible therapeutic approach to control the progression of AD.

Curcumin Improves Amyloid β-Peptide (1-42) Induced Spatial Memory Deficits through BDNF-ERK Signaling Pathway

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer’s disease (AD). However, the molecular mechanisms underlying curcumin’s effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer’s disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

BDNF gene polymorphisms are associated with Alzheimer's disease-related depression and antidepressant response.

Brain-derived neurotrophic factor (BDNF) is needed to support neuronal survival and differentiation. It also promotes synaptic remodeling and modulates the function of many other neurotransmitters. The current study examined potential association between single nucleotide polymorphisms (SNPs) of the BDNF gene (G11757 C, C270T, G196A, G-712A) and Alzheimers disease-related depression (AD-D). Participants included 336 patients with AD; 128 of these patients had AD-D. Response to 8-week paroxetine treatment was also assessed. The frequency of the 11757 C allele was significantly higher in AD-D than in the Alzheimers disease without depression (AD-nD) patients (p = 0.003 after Bonferroni correction). The 196A allele occurred with significantly higher frequency in AD-D patients (p = 0.001 after Bonferroni correction versus AD-nD). Carriers of the A allele of G196A responded better to paroxetine treatment. These findings support an important role of BDNF polymorphism in AD-D.

Development and Validation of a Risk-Score Model for Type 2 Diabetes: A Cohort Study of a Rural Adult Chinese Population

Some global models to predict the risk of diabetes may not be applicable to local populations. We aimed to develop and validate a score to predict type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. Data for a cohort of 12,849 participants were randomly divided into derivation (n = 11,564) and validation (n = 1285) datasets. A questionnaire interview and physical and blood biochemical examinations were performed at baseline (July to August 2007 and July to August 2008) and follow-up (July to August 2013 and July to October 2014). A Cox regression model was used to weigh each variable in the derivation dataset. For each significant variable, a score was calculated by multiplying β by 100 and rounding to the nearest integer. Age, body mass index, triglycerides and fasting plasma glucose (scores 3, 12, 24 and 76, respectively) were predictors of incident T2DM. The model accuracy was assessed by the area under the receiver operating characteristic curve (AUC), with optimal cut-off value 936. With the derivation dataset, sensitivity, specificity and AUC of the model were 66.7%, 74.0% and 0.768 (95% CI 0.760–0.776), respectively. With the validation dataset, the performance of the model was superior to the Chinese (simple), FINDRISC, Oman and IDRS models of T2DM risk but equivalent to the Framingham model, which is widely applicable in a variety of populations. Our model for predicting 6-year risk of T2DM could be used in a rural adult Chinese population.

Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics

Alzheimers disease (AD) is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

Secular trends in the prevalence of type 2 diabetes in adults in China from 1995 to 2014: A meta‐analysis

The aim of the present study was to estimate trends in the prevalence of type 2 diabetes mellitus (T2DM) in adults in China.

Promoter polymorphisms of SERPINE1 are associated with the antidepressant response to depression in Alzheimer's disease.

Depression is one of the most frequent neuropsychiatric symptoms in Alzheimers disease (AD). As the main regulator of the tissue plasminogen activator/brain-derived neurotrophic factor axis, plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of both AD and depression. This suggests a potential role of the PAI-1 gene SERPINE1 in the development of AD-related depression and its response to antidepressant treatment. The purpose of this study was to explore the association between the SERPINE1 promoter polymorphisms (rs1799889 and rs2227631) and the risk of depression in AD and to determine the relationship between these 2 polymorphisms and the response to paroxetine treatment in AD patients with depressive symptoms. A total of 423 AD patients, all of which were inpatients, including 161 patients with obvious depressive symptoms, were recruited into this study, and the MassARRAY system was used for genotyping. We failed to detect any significant associations of these 2 polymorphisms with AD-related depression in the Chinese population (p>0.05). However, for the depressive symptoms in AD, the frequency of the 5G allele of rs1799889 was significantly higher (p=0.009 after Bonferroni correction) in responders than in non-responders to an 8-week paroxetine treatment. Our preliminary results suggest that the SERPINE1 promoter polymorphisms may be associated with antidepressant treatment, but not with the increased susceptibility to the depressive symptoms in AD.

Effect of dynamic change in body mass index on the risk of hypertension: Results from the Rural Chinese Cohort Study

OBJECTIVES To examine the effect of change in body mass index (BMI) on incident hypertension by gender and age groups. METHODS A total of 10,145 non-hypertensive participants 18-75years old from rural areas in the middle of China were selected for this cohort study. Questionnaire interview and anthropometric and laboratory measurements were performed at baseline (during July to August 2007 and July to August 2008) and follow-up (during July to August 2013 and July to October 2014). Multiple logistic regression analysis was used to examine the relationship between change in BMI and incident hypertension. RESULTS During a mean follow-up of 6.03±0.69years, hypertension developed in 794 of 3986 men and 1184 of 6159 women. Both genders who were obese (BMI ≥28kg/m2 for Chinese people) at follow-up, regardless of their obesity status at baseline, showed greater risk of hypertension than those who were non-obese (BMI <28kg/m2) at both baseline and follow-up. We found a dose-response relationship between change in BMI and incident hypertension. Risk of hypertension was markedly greater with a BMI gain of the highest quartile or more as compared with a BMI reduction of the lowest quartile or more, except for women 60-75years old. CONCLUSIONS Risk of hypertension was high for non-hypertensive people in rural China with stable obesity. BMI dynamic gain may be related to incident hypertension for men of all ages and young and middle-aged women.

Botulinum Toxin A for the Treatment of a Child with SUNCT Syndrome

Background. Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome is an unusual cause of headache, mainly described in older adults, and is rare in children. Pain attacks may be severe, frequent, and prolonged. The therapeutic benefits of many drugs are disappointing. Patient and Methods. A 12-year-old boy suffered severe headache and toothache for 20 days. As treatment with nonsteroidal anti-inflammatory drugs, anticonvulsants, and steroids proved ineffective, he was treated with ipsilateral multisite subcutaneous injections of botulinum toxin A 70 U around the orbit, the temporal area, and the upper gum. Results. The pain had reduced in frequency and severity by the fourth day after treatment and had completely disappeared after 7 days. There were no side effects or recurrence during a subsequent 17-month follow-up period. Conclusion. Botulinum toxin A can be used to treat the first episode of SUNCT in children over the age of 12 years.

Risk of type 2 diabetes mellitus associated with plasma lipid levels: The rural Chinese cohort study

AIM To investigate the association of type 2 diabetes mellitus (T2DM) risk and plasma lipid levels in rural Chinese. METHODS Each lipid variable was divided into quartiles and dichotomized by clinical cutoff points. Cox proportional-hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of T2DM risk and plasma lipid levels and explore the interaction between plasma lipid levels and other risk factors. RESULTS 11,929 participants were included in the analysis. We documented 720 incident cases of T2DM over 70,720.84 person-years of follow-up, for an incidence of 10.18/1,000 person-years. In the multivariable-adjusted model, risk of T2DM was increased with the highest versus lowest quartiles of total cholesterol (TC) and triglycerides (TG) levels and TC/high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratios. The HRs (95% CIs) for the fourth quartiles, for example, were 1.34 (1.03-1.74), 2.32 (1.73-3.13), 1.66 (1.23-2.25), and 1.84 (1.38-2.45), respectively. In addition, risk of T2DM was increased with high TG level and TC/HDL-C and TG/HDL-C ratios by clinical cutoffs. The HRs (95% CIs) were 1.50 (1.25-1.80), 1.24 (1.03-1.48), and 1.44 (1.18-1.75), respectively. Risk of T2DM was associated with interactions between all lipid variables and age and BMI. TG level and TG/HDL-C ratio additionally interacted with gender (all Pinteraction < 0.0001). CONCLUSIONS Risk of T2DM was increased with elevated serum levels of TC and TG and TC/HDL-C and TG/HDL-C ratios and also with interactions between high TC and TG levels and TC/HDL-C and TG/HDL-C ratios and age and BMI in a rural Chinese population.