How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics

Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut–brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota–gut–brain axis.     

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.     

Resolving Apparent Contradictions Concerning the Relationships Among Fear or Anxiety and Aggression During Lactation: Theoretical Comment on D'Anna, Stevenson, and Gammie (2005).

Pregnancy and lactation involve dramatic changes in behavior and physiology necessary for the successful production and sustenance of offspring. This requires numerous processes to emerge and be coordinated in a finely tuned manner. Reduced corticotropin releasing factor (CRF) receptor activity and hypothalamic-pituitary-adrenal function are thought to be involved in numerous functions during lactation, such as reducing fear and anxiety, which in turn, is proposed to disinhibit aggressive behaviors. K. L. D'Anna, S. A. Stevenson, and S. C. Gammie (2005) reported that central infusion of urocortin 1 and 3, anxiogenic peptides that bind to CRF receptors, reduce maternal aggression in lactating mice and alter neural c-fos expression. However, the relationship between stress hormones and where they act, emotional state, and aggression during lactation is complicated, and our understanding of how these factors influence each other might benefit from a comprehensive reevaluation of these literatures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High,in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic,in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus

Extracellular adenosine 5′-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans.     

东营凹陷沙河街组层序地层对成岩的控制作用

东营凹陷发育了沙四段底界面(T 7)、沙四段与沙三段分界面(T′6)及沙二下亚段顶界面(T′2)等3个二级层序界面。根据对储集层成岩作用的深入研究发现,原有的埋藏成岩作用序列不仅受深度的影响,而且受此层序地层所控制,在层序界面附近和层序体内部存在一定的规律性。据此确定了层序界面附近发育的淋滤、溶解成岩相带和层序体内部发育的黏土矿物转换和化学胶结成岩相带。认识到层序界面通常是流体运移的通道,影响界面上下低水位体系域和高水位体系域内储集层的成岩相展布,对改善储集层储集性能有利;层序体内部储集层成岩差异性明显,储集性往往受到制约。     

琼北新生代火山作用与构造环境

海南岛北部广泛分布的新生代火山岩，严格受“雷琼坳陷带”边界的控制，其中碱性玄武岩系列的岩石，主要分布在坳陷带边部，形成于上第三纪；拉斑玄武岩系列的岩石，主要分布在坳陷带中心部位，形成于第四纪。玄武岩以富Ｋ，Ｐ，Ｒｂ，Ｚｒ，Ｓｒ，Ｂａ，Ｔｈ，Ｔａ，Ｎｂ，ＬＲＥＥ，贫Ｙ及Ｙ／Ｎｂ＜１为特征，显示板内大陆裂谷岩浆作用的特点。     

电化学调控法抑硫浮选的研究

进行了电化学法抑硫浮选的研究，探索了化学试剂法和外控电位法对细粒煤浮选脱硫的影响，通过试验证实，在低的矿浆电位下，黄铁矿能被有效抑制，提高了脱硫效率，它是一种经济有效、简单而无污染的抑制黄铁矿的新方法．     

试论湖南涟源凹陷中新生代构造应力场

本文依据实测的构造要素和盆地分析,恢复了涟源凹陷中生代以来六期不同体制的构造应力场,讨论了该区构造应力场与盖层构造形成和发展的关系。印支期以北西-南东向挤压为主,奠定了盖层构造基本格架;燕山-喜山期北西-南东向伸展与挤压交替进行,使盖层构造复杂化。     

Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview,Technical Development,and Measures of Peripheral Activation in Adolescent Patients

The NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome is a node of intracellular stress pathways and a druggable target which integrates mitochondrial stress and inflammatory cascades. While a body of evidence suggests the involvement of the NLRP3 inflammasome in numerous diseases, a lack of reliable measurement techniques highlights the need for a robust assay using small quantities of biological samples. We present a literature overview on peripheral activation of the NLRP3 inflammasome in mood disorders, then outline a process to develop and validate a robust assay to measure baseline and activated intracellular levels of “apoptosis-associated speck-like protein containing a CARD” (ASC) as a key component of an inflammatory profile in peripheral blood mononuclear cells (PBMC). A consistent association between high NLRP3 mRNA levels and relevant cytokines was seen in the literature. Using our method to measure ASC, stimulation of PBMC with lipopolysaccharide and nigericin or adenosine triphosphate resulted in microscopic identification of intracellular ASC specks, as well as interleukin 1 (IL-1) beta and caspase-1 p10 in the periphery. This was abolished by dose-dependent pre-treatment with 100 nM MCC950. We also report the use of this technique in a small pilot sample from patients with bipolar disorder and depressive disorders. The results show that levels of intracellular ASC and IL-1 beta are sensitive to change upon activation and maintained over time, which may be used to improve the detection of NLRP3 activation and guide personalized therapeutic strategy in the treatment of patients.     

Advance application of Raman spectroscopy for quantitative analysis of noncrystalline components in thin films of poly(ε-caprolactone)/poly(butadiene) blends

A quantitative analysis method for the distribution of noncrystalline poly(butadiene) component in poly(ε-caprolactone)/poly(butadiene) (PCL/PB) binary blends have been analyzed by advance application of Raman spectroscopy, optical microscopy, and differential scanning calorimetry (DSC) techniques. Thin films of different compositions of PCL/PB binary blends were prepared from solution and isothermally crystallized at a certain temperature. After calibration with real data, quantitative analyses by Raman spectroscopy revealed the amorphous PB are trapped inside the PCL crystals. Polarized optical microscopy and real time atomic force microscopy were used to collect data for the crystal morphology and crystal growth rate. For pure PCL crystals, a morphology of truncated lozenge shape was observed, independent of crystallization temperature and regardless of the blends compositions. For the pure PCL and their blends, almost unique crystal growth rate was found. The miscibility behaviors using DSC were drawn through melting point depression method. The Hoffman-Weeks extrapolations of the blends were found to be linear and identical with those of the neat PCL. The interaction parameter for the blends indicating that the PCL and PB blends have no intermolecular interaction, confirming the blends are immiscible. Despite the immiscibility of the blend, the PCL crystals do not bend during the growth process and do not reduce the growth rate as they do for miscible blend systems.