抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

基礎講座 電気泳動(Electrophoresis)

Differential early effects of traumatic brain injury on spike-wave discharges in Sprague-Dawley rats

Пластичность нервной системы при ее формировании в процессе развития, репарации сетей и отдельных нейронов после повреждения, модификации синаптических и нейронных связей в процессе нормального функционирования реализуется на основе высококоординированных паттернов нейронной активности. Фундаментальным компонентом зависимой от активности пластичности, регулирующей функционирование нейронных сетей, являются синхронизированные ритмические разряды нейронных ансамблей. H. Scharfman [1] предложила рассматривать эпилепсию как важнейший пример нейропластичности. Обсуждая нейробиологические субстраты эпилепсии, она отметила целый ряд феноменов, подтверждающих удивительную способность мозга изменять свои основные структуры и функции. Некоторые из этих изменений кратковременны, но очень ярко выражены, другие долговременны и могут продолжаться годами. Например, гранулярные клетки зубчатой извилины гиппокампа подвергаются существенным изменениям в результате судорожной активности. Автор заключает, что едва ли не лучшие примеры для изучения нейропластичности можно обнаружить именно при исследовании эпилепсии в эксперименте и клинике. За последние 3 десятилетия сформировалось мнение об аберрантной пластичности, лежащей в основе патогенеза всех форм эпилепсии. Сформулированное Y. Ben-Ari утверждение «судороги порождают судороги» («seizures beget seizures») требовало понимания того, почему и как именно это происходит, т.е. исследования механизмов

[Neuronal plasticity and epilepsy: modern concepts and mechanisms of epilepsy and depression comorbidity].

Opiate dependence results from impairments of neuronal plasticity, i.e., so-called aberrant neuroplasticity, formation of which involves long-term structural-functional rearrangements persisting even during drug abstinence. Nitric oxide (NO) is involved both in mediating the effects of opiates and in the mechanisms of some types of neuroplasticity, so NO may potentially take part in the development of psychopathological processes on opiate withdrawal. The present study addressed measures of the nitrergic system (nitric oxide synthase (NOS) activity and nitrite and nitrate (NO
 x
 −
 ) concentrations) in areas of the rat brain; anxiety was also assessed, in terms of behavioral measures in the elevated plus maze, during morphine withdrawal. NOS activity was found to increase by day 3, while the NO
 x
 −
 concentration was increased by day 6 of withdrawal, these changes being seen only in the hippocampus. At six days after morphine withdrawal, rats showed more entries into the open arms of the elevated plus maze and remained in these arms longer. Correlations were found between measures of the NO system in the hippocampus and the behavior of the animals in the maze. These results suggest that changes in the activity of the nitrergic system in the hippocampus represent one of the molecular mechanisms impairing the behavior of animals in abstinence.

Changes in anxiety in abstinence correlate with the state of the nigrostriatal system in the rat hippocampus.

We studied the effects of the proteolytic enzymes caspase-3 and calpain on the changes in LTP-dependent modifications of paired plasticity in the CA1 field of hippocampal slices. Paired pulse facilitation (PPF) was measured for 1 h after high-frequency stimulation of Schaffer collaterals (100 Hz, 1 s). After LTP induction, we observed a significant decrease in PPF, whereas when LTP was not induced after tetanization a decrease in PPF was also absent. At 1 hour after tetanization, the residual decline in PPF significantly correlated with the efficacy of LTP maintenance. After the end of the experiments we measured the activity of caspase-3 and calpain in the same slices. Potentiation rarely occurred with the low activity of both enzymes and most often came to the end with depression. The probability of LTP induction did not depend on specific activation of any proteases; however, the probability of long-term maintenance of the modifications was significantly higher when the activity of caspase-3, but not of calpain, was elevated. High activity of both proteases simultaneously did not influence the probability of LTP induction; however, under these conditions, LTP maintenance was worse compared to the slices with higher activity of caspase-3. The effect of an LTP-dependent long-term decrease in PPF was predominant in slices with high activity of caspase-3. In contrast, a high activity level of calpain was associated with a less expressed and short-term decrease in PPF. A low activity level of calpain was related to a stable decrease in PPF after LTP induction. Both these effects disappeared under the conditions of high activity of both proteases. In these slices, potentiation was followed by a gradual PPF increase without its initial decrease. Analysis using “caspase-3,” “calpain,” and “LTP maintenance” as factors revealed a significant interaction between the factors. Our data suggest that caspase-3 promotes whereas calpain prevents the maintenance of presynaptic mechanisms of plasticity. The specific effects of proteases may be related to different loci of plasticity or concurrent interaction in the presynaptic zone.

Caspase-3 and calpain: Differently directed involvement in presynaptic long-term plasticity

In this theoretical study, the concept of connectome and connectopathy was used for the analysis of the data related to molecular mechanisms of the pathogenesis and comorbidities of neurological and psychiatric diseases (in particular, depression), as well as approaches to their pharmacotherapy. A scheme of main network levels underlying connectome is provided, including subcellular and molecular levels. Neuronal networks forming connectome are based on several 'lower' network levels, the state and interactions of these levels stipulating the state and functioning of the connectome as well as its dynamic changes. Similarly, network levels are demonstrated for connectopathies. Common network mechanisms of connectopathies, particularly depressive disorders and neurodegenerative diseases, are not only underlying the comorbidity, but also suggest common potential pharmacotherapeutic approaches.

Natalia V. Gulyaeva

Papers

Differential early effects of traumatic brain injury on spike-wave discharges in Sprague-Dawley rats

[Neuronal plasticity and epilepsy: modern concepts and mechanisms of epilepsy and depression comorbidity].

Changes in anxiety in abstinence correlate with the state of the nigrostriatal system in the rat hippocampus.

Caspase-3 and calpain: Differently directed involvement in presynaptic long-term plasticity

[Cerebral plasticity and connectopathies: mechanisms of comorbidity of neurological diseases and depression].