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Объем 1, Проблема 2 (2013)

Обзорная статья

A Role for Microglia in Repeated Stress-Induced Functional Changes in the Medial Prefrontal Cortex in Rodents

Shiho Kitaoka and Tomoyuki Furuyashiki

In rodents, repeated stress alters the function of the medial prefrontal cortex (mPFC), associated with dendritic atrophy and synaptic loss, leading to emotional and cognitive changes. Roles for monoamines, namely dopamine and noradrenaline, have been implicated in this process. Thus, dopaminergic activity in the mPFC confers stress resilience, and repeated social defeat stress attenuates this dopaminergic activity, leading to social avoidance. In contrast, the activation of adrenergic receptors promotes emotional and cognitive changes induced by repeated stress. Especially, adrenergic signaling in the mPFC during stress exposure is critical for a decline in an mPFC-dependent behavioral performance after repeated stress. Repeated stress activates microglia in multiple brain areas, and recent studies have suggested a link between microglial activation and monoaminergic functions in repeated stress. For example, blockade of β-adrenergic receptors impairs microglial activation by repeated stress. It has also been suggested that stress-activated microglia release prostaglandin (PG) E2 , an inflammation-related molecule that attenuates mPFC dopaminergic activity and causes behavioral depression. Recent studies in non-stressed mice have shown that microglial processes can directly contact with neuronal structures in an activity-dependent manner, leading to structural remodeling of neurons. Since repeated stress activates microglia in multiple brain areas including the mPFC, we hypothesize that microglia may play direct and indirect roles in stress-induced alteration in mPFC functions

Редакционный

Importance of Studying and Discussing the Management of Complications During Neurosurgical Procedures

Homajoun Maslehaty and Athanasios K Petridis

The neurosurgical training is one of the most demanding ones. Studying and mastering the anatomy of the human central nervous system, reading and understanding scientific papers, learn how to perform surgeries, which can bring the surgeon to its limits day for day, are three equal columns in the making of a good neurosurgeon. Except of studying surgeries and books and learning from grand masters the study of some ones own surgeries and own mistakes become more and more important. Video recording of the surgeries and identifying the possible mistakes are very effective in order to correct future mistakes. Which step has led to a complication and how the complication was managed in a “self-made” video record proved, at least for us, to be a very effective way to improve surgical skills.

исследовательская статья

Treating Parkinson Disease with Adult Stem Cells

Henry E Young, Lee Hyer, Asa C Black Jr and Joe Sam Robinson Jr

Parkinson disease affects ~2% of all people 70 years of age and older. People with Parkinson disease exhibit excessive shaking (tremors) at rest, loss of mental function, loss of involuntary function, and psychiatric problems. A proposed experimental cure for Parkinson disease is the transplantation of healthy nerve cells into the brain. It has been proposed that these nerve cells be taken from either aborted fetuses or derived from embryonic stem cells. Due to ethical and moral issues that proposal will probably not become a reality. Endogenous adult totipotent stem cells and adult pluripotent stem cells are very similar to embryonic stem cells. These primitive adult stem cells will form neurons, glia, skin, muscle, fat, cartilage, bone, blood vessels, blood cells, liver cells and pancreas cells under the appropriate inductive conditions. The current report proposes the use of adult totipotent stem cells for the treatment of Parkinson disease. As a test of this proposal, adult totipotent stem cells were utilized in a bedside clinical autologous phase-0 efficacy trial in adult humans with Parkinson disease. The results from this study suggested an efficacious response utilizing adult totipotent stem cells as a treatment modality for Parkinson disease.

исследовательская статья

Diurnal Spatial Rearrangement of Microglial Processes through the Rhythmic Expression of P2Y12 Receptors

Yoshinori Hayashi, Satoru Koyanagi, Naoki Kusunose, Fumiko Takayama, Ryo Okada, Zhou Wu, Shigehiro Ohdo and Hiroshi Nakanishi

Microglia plays important roles in synaptic reorganization during the postnatal developmental stage. Moreover, microglia continuously surveys the functional state of the synapse and change to improve the function. This phenomenon was attributed to the fine process of extension and retraction. However, the mechanism underlying the dynamics of microglial movement and function is still unclear. We herein report that cortical microglia exhibit clock gene-regulated diurnal morphological changes. Cortical microglia extended their processes during the dark phase and retracted them during the light phase. These diurnal changes were also observed in cortical microglia from animals housed under constant darkness, but not in cortical microglia from clock-mutant mice. The mean contact ratio of the microglia-synapse interactions was significantly larger during the dark phase than the light phase. These diurnal changes in microglial morphology and microglia-synaptic interactions were significantly inhibited by the systemic administration of clopidogrel, a P2Y12 receptor (P2Y12R) blocker. We further observed diurnal variation in the P2Y12R expression in cortical microglia. The reporter analyses further revealed that P2Y12R was regulated by a negative feedback loop of the clock system. These observations suggest that the microglial clock system drives the diurnal morphological changes of microglia and microglia-synapse interactions by controlling the P2Y12R expression.

исследовательская статья

Epstein-Barr Virus, Hygiene, and Multiple Sclerosis in Mexico City

Jennifer Massa, Simon KC, Lopez-Ridaura, Rivera-Flores J, Silverman-Retana O, Corona T, Kagan IG and Ascherio

Background/Aims: We studied whether serological antibody titers against Epstein-Barr virus (EBV) were related to multiple sclerosis (MS) risk in Mexico City, a population undergoing an epidemiological transition. Additionally, we explored the association between markers of hygiene and intestinal parasite infection and MS prevalence.

Methods: We conducted a hospital based case-control study in Mexico City; 52 incident MS cases. Childhood and adult hygiene scores were created using information from questionnaires. 51 cases and 51 controls provided blood samples for biomarker analyses.

Results: There was a 3-fold increase in risk of MS with each 1 unit increase in anti-EBNA1 titer (OR 3.02, 95% CI: 1.01-9.02). Increasing childhood and adult hygiene scores were associated with a modestly increased risk of MS (ORchildhood 1.20, 95% CI: 1.04-1.38; ORadult 1.28, 95% CI: 1.04-1.58). We found no association between antibody titer to neither Stronglyloides nor Ascaris and MS risk.

Conclusion: High anti-EBNA1 antibody titers appears to be associated with increased MS risk even in a region where MS had historically low incidence and infectious mononucleosis is rare, providing further support for the postulated role of EBV in MS etiology. We also found moderate support for a role of higher ‘hygiene’ being associated with susceptibility to MS.

исследовательская статья

Ginkgo Biloba Extract Protects Substantia Nigral Neurons from Apoptosis in PD Rat Model

Cao Fei, Luo Fang, Zhang Lei, Su Ying, Chen Li, Hu Bo and Tong E-tang

Purpose: To investigate the apoptotic mechanism during the pathological process of Parkinson disease (PD) and explore the availability of Ginkgo biloba extract (EGb) to cure PD.

Methods: Followed 6-OHDA injection stereotaxically to right side of substantia nigra pars compacta(SNc), at the date of 1, 7,14 and 21, we used biochemical, immunohistochemical, TUNEL and electron microscopic techniques to evaluate the level of apoptosis (TUNEL), monitor the degree of oxidative reaction (MDA.SOD), and to observe the change of ultrastructure of substantia nigra in the experimental PD models of rats (PD group), the EGb treatment group (EGb group) and the control group. Results: Contrast to the Control group, the number of apoptotic neurons and free radical level increased in the PD group and the EGb group, but the PD group surpassed the EGb group (p<0.05).In the PD group, the ultrastructure of substantia nigra exhibited the morphological characteristics of apoptosis from 1d to 21d.

Conclusions: Free radical insult contributes to the pathological process of PD in rats. EGb may ameliorate the injury of substantia nigra through expiring free radicals during the pathological process of PD in rats.

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