DISC1 localizes to the centrosome by binding to kendrin

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with major mental disorders in a Scottish family. Using the yeast two-hybrid system, we screened a human brain cDNA library for interactors of the DISC1 protein. One of the positive clones encoded kendrin/pericentrin-B, a giant protein known to localize specifically to the centrosome. The interaction between DISC1 and kendrin in mammalian cells was demonstrated by an immunoprecipitation assay. Residues 446-533 of DISC1 were essential for the interaction with kendrin. Immunocytochemical analysis revealed the colocalization of DISC1 and kendrin to the centrosome. These data indicate that DISC1 localizes to the centrosome by binding to kendrin. Kendrin has been reported to anchor the gamma-tubulin complex to the centrosome, providing microtubule nucleation sites. The present study suggests the possible involvement of DISC1 in the pathophysiology of mental disorders due to its putative effect on centrosomal function.     

Statistics for disinterested scientists.

This paper presents a brief introduction to some basic statistical tools and techniques with examples applied to biological data. Perhaps after becoming more familiar with statistics and more appreciative of their power in extracting information from data the previously fearful and skeptical researcher may be more inclined to make them an integral part of his research technique and also include them in his publications. For problems of greater difficulty, consultation at the early stages, preferably before undertaking the project, with a good biostatistician is suggested.     

SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common cause of dementia among the elderly. Efforts have been made to understand the genetic and epigenetic mechanisms involved in the development of this disease. As SORL1 (sortilin-related receptor) and SIRT1 (sirtuin 1) genes have been linked to AD pathogenesis, we aimed to investigate their mRNA expression and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly subjects and AD patients. We also evaluated these levels in peripheral blood leukocytes from young, healthy elderly and AD patients, investigating whether there was an effect of age on these profiles. The comparative CT method by Real Time PCR and MALDI-TOF mass spectrometry were used to analyze gene expression and DNA methylation, respectively. SORL1 gene was differently expressed in the peripheral blood leukocytes and might act as a marker of aging in this tissue. Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups. The impact of these studied genes on AD pathogenesis remains to be better clarified.     

Leisure activities, cognition and dementia

Accumulated evidence shows that leisure activities have a positive impact on cognitive function and dementia. This review aimed to systematically summarize the current evidence on this topic taking into account the limitations of the studies and biological plausibility for the underlying mechanisms linking cognition, dementia and leisure activities, with special attention on mental, physical and social activities. We included only longitudinal studies, with a follow-up time of at least 2 years, published in English from 1991 to March 2011 on leisure activities and cognition (n = 29) or dementia (n = 23) and provided some evidence from intervention studies on the topic. A protective effect of mental activity on cognitive function has been consistently reported in both observational and interventional studies. The association of mental activity with the risk of dementia was robust in observational studies but inconsistent in clinical trials. The protective effect of physical activity on the risk of cognitive decline and dementia has been reported in most observational studies, but has been less evident in interventional studies. Current evidence concerning the beneficial effect of other types of leisure activities on the risk of dementia is still limited and results are inconsistent. For future studies it is imperative that the assessment of leisure activities is standardized, for example, the frequency, intensity, duration and the type of activity; and also that the cognitive test batteries and the definition of cognitive decline are harmonized/standardized. Further, well designed studies with long follow-up times are necessary. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Supporting the generalist genes hypothesis for intellectual ability/disability: the case of SNAP25

Intellectual disability (ID) is an unresolved health care problem with a worldwide prevalence rate of 2–3%. For many years, research into the genetic causes of ID and related disorders has mainly focused on chromosomal abnormalities or X‐linked genetic deficits. Only a handful of autosomal genes are known to cause ID. At the same time it has been suggested that at least some cases of ID represent an extreme form of normal intellectual ability and therefore that genes important for intellectual ability in the normal range may also play a role in ID. In this study, we tested whether the autosomal SNAP25 gene, which was previously associated with variation in intellectual ability in the normal range, is also associated with ID. The gene product of SNAP25 is an important presynaptic plasma membrane protein, is known to be involved in regulating neurotransmitter release, and has been linked to memory and learning by its effect on long term potentiation in the hippocampus. Allele frequencies of two genetic variants in SNAP25 previously associated with intellectual ability were compared between a group of 636 ID cases (IQ < 70) and a control group of 361 persons of higher than average intellectual ability. We observed a higher frequency of the putative risk allele of rs363050 (P = 0.02; OR = 1.24) in cases as compared to controls. These results are consistent with a role of SNAP25 in ID, and also support the notion that ID reflects the lower extreme of the quantitative distribution of intellectual ability.     

成年女性压力性尿失禁患者心理健康状况调查分析

目的:探讨成年女性压力性尿失禁患者的心理健康状况,提出护理干预方法。方法:采用SCL-90及自编一般资料,对浏阳市市区80名有压力性尿失禁症状的成年女性进行心理健康自评调查,另80名无压力性尿失禁症状的成年女性为对照。结果:有压力性尿失禁症状的成年女性SCL-90总分、阳性项目数、阳性项目均分及躯体化、人际关系、抑郁、焦虑、敌对、恐怖和精神病性等因子评分均明显高于对照组及常模组(P<0.05)。结论:成年女性压力性尿失禁患者心理健康状况不容乐观,应引起重视,并对其进行护理干预,加强对她们的心理疏通,可以提高疾病的防治效果。     

Lysophosphatidylcholine induces delayed myelination in the juvenile ventral hippocampus and behavioral alterations in adulthood

Maternal virus infection or maternal polyinosinic-polycytidilic acid injection confers behavioral alterations including deficit in prepulse inhibition on the offspring. We previously found delayed myelination specifically in the early postnatal hippocampus in the polyinosinic–polycytidilic acid-injection model. To test whether the transient delay in myelination in the juvenile hippocampus leads to abnormal behaviors after adolescence, we injected lysophosphatidylcholine, a potent demyelinating agent, into the ventral hippocampus of the 10-day-old rat. The lysophosphatidylcholine treatment yielded hypomyelination at postnatal day 16, but myelination reverted to normal level in the adult rat. Neuronal arrays and morphology were not disturbed in this model. We then performed a battery of behavioral tests on the lysophosphatidylcholine-treated and control PBS-injected rats. The lysophosphatidylcholine-treated rats showed deficit in prepulse inhibition, motor hyperactivity in response to methamphetamine and anxiety-related behaviors, all of which are typical behaviors observed in the maternal infection models. These findings suggest that the timing of myelination in the early postnatal hippocampus is crucial for the proper development of sensorimotor and emotional functions. The lysophosphatidylcholine-treated rat without a gross anatomical defect is useful as a model for psychotic disorders.     

Endogenous opiates: 2000

This paper is the twenty-third installment of the annual review of research concerning the opiate system. It summarizes papers published during 2000 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunological responses.     

Lipid Binding Defects and Perturbed Synaptogenic Activity of a Collybistin R290H Mutant That Causes Epilepsy and Intellectual Disability

Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the Cb^R290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans.     

优质护理模式对心肌梗死康复期患者心理障碍及不良情绪的影响研究

目的:研究优质护理模式对心肌梗死康复期患者心理障碍及不良情绪的影响程度,旨在为康复期患者护理方式的选取提供理论依据。方法:将本院2014年1月~2014年12月的70例心肌梗死康复期患者遵照随机数字表法分为对照组和观察组各35例,对照组采用常规的康复护理进行干预,观察组则以优质护理理念为指导进行护理干预,然后将两组护理前和护理后2周、4周及8周的心理障碍及不良情绪状态采用SECD6量表及HAD量表进行评估,并将评估结果进行比较。结果:观察组护理后2周、4周及8周的SECD6量表及HAD量表评估结果均明显优于对照组,P均0.05,均有显著性差异。结论:优质护理模式对心肌梗死康复期患者治疗信心及不良情绪的影响相对更为积极,为患者康复治疗的顺利进行奠定了基础。