Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Silver impregnation applied to striated muscle: The sarcoplasmic reticulum

The classical black reaction developed by Camillo Golgi is shown to impregnate the tubules and fenestrations of the sarcoplasmic reticulum (SR) in striated muscle. This is a double impregnation of chromate and silver, which usually fills extracellular spaces. The method is difficult insofar as long incubation times are required, and location of the successfully “stained” SR in plastic-embedded tissue blocks is unpredictable. The light microscope is absolutely necessary to find the good regions which can then be cut from the blocks in 1-μm-thick sections and examined in the electron microscope. Stereo pairs give the best results since these resolve overlap problems common to thick sections. A variety of artifacts are illustrated which can help avoid erroneous interpretations. The Golgi-“stained” SR shows this elusive network with unsurpassed contrast and should benefit the morphological studies of muscle-membrane enthusiasts.     

Age and gender differences in cardiac reactivity and subjective emotion responses to emotional autobiographical memories.

This research reports age and gender differences in cardiac reactivity and subjective responses to the induction of autobiographical memories related to anger, fear, sadness, and happiness. Heart rate (HR) and subjective state were assessed at baseline and after the induction of each emotion in 113 individuals (61 men, 52 women; 66% European American, 34% African American) ranging in age from 15 to 88 years (M = 50.0; SD = 20.2). Cardiac reactivity was lower in older individuals; however, for anger and fear, these age effects were significantly more pronounced for the women than the men. There were no gender differences in subjective responses, however, suggesting that the lower cardiac reactivity found among older people is dependent on gender and the specific emotion assessed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predicting Acute Renal Failure after Cardiac Surgery: Validation and Re‐definition of a Risk‐Stratification Algorithm

Background:  Acute renal failure (ARF) after cardiac surgery is associated with significant morbidity and mortality, irrespective of the need for dialysis. Previous studies have attempted to identify predictors of ARF and develop risk stratification algorithms. This study aims to validate the algorithm in an independent cohort of patients that includes a significant proportion of female and black patients and compares two different definitions of renal outcome.
Methods:  A large single center cardiac surgery database was examined (n, 24,660; 1993–2000) which included 29.9% females and 3.7% black patients. Post‐operative ARF was defined as: a) ARF requiring dialysis, b) > 50% reduction in creatinine clearance relative to baseline or requiring dialysis. Clinical variables related to baseline renal function and cardiovascular disease were used in recursive partitioning analysis for both outcome definitions. Chi‐square goodness of fit analysis was performed to validate the algorithm.
Results:  The frequency of post‐operative ARF requiring dialysis ranged between 0.5 and 15.5% based on the risk categories with the area under the receiver operating characteristic (ROC) curve of 0.78. Using the more inclusive definition of ARF, the frequency was significantly higher ranging from 2.6 to 25%(P < 0.001) with an area under ROC curve of 0.65.
Conclusions:  The renal risk stratification algorithm is valid in predicting post‐operative ARF in an independent cohort of patients, well represented by differences in gender and race. Since the need for dialysis remains subjective, a more objective and inclusive definition of ARF may help in identifying a larger number of patients 'at‐risk'.     

Behavioral depression during cocaine withdrawal is associated with decreased spontaneous activity of ventral tegmental area dopamine neurons.

Withdrawal from an escalating-dose, bingelike regimen of cocaine administration in rats produced significantly depressed levels of locomotor activity during the nocturnal portion of the day-night cycle. This effect was observed during the first 48 hrs of testing. Extracellular single-unit recordings of ventral tegmental area (VTA) dopamine (DA) neurons revealed no differences between saline- and cocaine-treated rats with respect to basal firing rates. However, significantly fewer spontaneously active VTA DA neurons were encountered in rats withdrawn from binge cocaine. As with the nocturnal hypoactivity, this effect was observed only during the first 48 hrs of withdrawal. These findings suggest that short-term DA neuron dysfunction during cocaine withdrawal temporally corresponds to behavioral disruptions that are similar to those described in human addicts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"The association between emotional upset and cardiac arrhythmia during daily life": Correction to Carels et al. (2003).

Reports an error in the original article by R. A. Carels et al (Journal of Consulting & Clinical Psychology, 2003[Jun], Vol 71[3], 613-618). On page 615, Lines 18, 20, 22, of Table 1, the data in the rows that read "Tachycardia in min per hr," "Repetitive PVCs per hr," and "PVCs per hr" are incorrectly reported in the n and % columns. They should have been reported in the M and SD columns. The corrected table is provided. (The following abstract of this article originally appeared in record 2003-00756-023.) Ventricular arrhythmia exhibits considerable within-subject variability that cannot be attributed to clinical status alone. This investigation examined the extent to which cardiac arrhythmia was associated with psychological and physical factors assessed during the hour preceding arrhythmic or nonarrhythmic activity. Approximately twice hourly, 46 patients randomly completed a diary assessing mood and physical symptoms during 24-hr electrocardiographic monitoring. Greater negative emotion was associated with increased arrhythmia. Additionally, greater negative emotion was significantly associated with increased arrhythmia among participants in a low left ventricular ejection fraction group (LVEF). However, this relationship between negative emotion and arrhythmia was not... (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

基于HH模型的心肌细胞电模型

提出了一种心肌细胞电生理模型的建模仿真方法。通过借助Hodgkin-Huxley模型对单个心肌细胞建立细胞膜的等效电路模型,利用四阶Rouge-Kutta算法,研究并分析了心肌细胞膜内外离子电流及电位差变化。然后用C语言完成了对细胞膜等效电路模型的编程,利用Matlab软件平台进行了计算机仿真,得到了心肌细胞电生理学模型在不同刺激下的仿真实验结果。     

针对肌肉功能障碍患者的数据库研究与开发

建立标准数据库是临床研究病情变化的重要手段,建立适用于肌肉功能障碍患者的标准数据库模板更具有重要临床意义。本研究针对临床上所采集的具有肌肉功能障碍患者的肌力、肌电数据,通过ODBC连接方式,引入了统一建模语言(UML),使用VC++开发工具,设计和完成了Access数据库,以对获取到的大量的肌力、肌电数据进行管理和使用。数据库有效存储并管理肌力、肌电数据,同时能减少数据占有空间和数据冗余,它更好地满足了医院康复科的需求。