scholarly journals Allogenicity Boosts Extracellular Vesicle–Induced Antigen-Specific Immunity and Mediates Tumor Protection and Long-Term Memory In Vivo

2019 ◽  
Vol 203 (4) ◽  
pp. 825-834 ◽  
Author(s):  
Pia Larssen ◽  
Rosanne E. Veerman ◽  
Gözde Güçlüler Akpinar ◽  
Stefanie Hiltbrunner ◽  
Mikael C. I. Karlsson ◽  
...  
Author(s):  
О.А. Соловьева ◽  
М.А. Грудень ◽  
И.А. Калинин ◽  
А.М. Ратмиров ◽  
В.В. Шерстнев

Одним из важнейших патогенетических звеньев развития синуклеинопатий - группы хронических нейродегенеративных заболеваний, таких как болезнь Паркинсона, деменции с тельцами Леви и других является гиперпродукция белка α-синуклеина с последующей его агрегацией и образованием различающихся по размеру и структуре амилоидогенных форм белка, которые инициируют гибель нервных или глиальных клеток. В настоящее время для более полного понимания происходящих in vivo патологических процессов актуально изучение на моделях животных поведенческих эффектов как нативного белка α-синуклеина, так и его отдельных амилоидогенных структур (олигомеров и фибрилл), полученных и охарактеризованных in vitro, а также композиционных смесей данных белковых конформаций. Целью данной работы явилось изучение влияния композиционной смеси нативного белка α-синуклеина и олигомеров α-синуклеина при хроническом интраназальном введении на двигательную активность, кратковременную и долговременную память, а также тревожность стареющих мышей. Методы. Опыты проводили на 12- месячных самцах мышей C57Bl/6, которым на протяжении 14 дней один раз в сутки вводили отдельно в каждую ноздрю раствор α-синуклеина и его олигомеров, либо физиологический раствор. В тестах «Открытое поле», «Распознавание нового объекта», «Условная реакция пассивного избегания» и «Приподнятый крестообразный лабиринт» оценивали двигательную активность, кратко- и долговременную память, и тревожность животных. Результаты. Показано, что исследованная композиционная смесь конформаций α-синуклеина не вызывает статистически значимых изменений регистрируемых поведенческих показателей у стареющих мышей. Вместе с тем, ранее нами было документировано, что в условиях аналогичного экспериментального протокола нативный α-синуклеин инициирует снижение двигательной активности, а олигомеры α-синуклеина - угнетение двигательной активности, нарушение долговременной памяти и тревожности животных. Заключение. Полученные результаты свидетельствуют о менее выраженных поведенческих эффектах композиционной смеси нативной и олигомерной форм α-синуклеина, по сравнению с отдельными ее компонентами. Рассматриваются возможные механизмы выявленных особенностей влияния исследованной композиционной смеси конформаций α-синуклеина на поведенческом уровне. One of the most important steps in the pathogenesis of synucleinopathies, a group of chronic neurodegenerative diseases, such as Parkinson’s disease, dementia with Lewy bodies and others, is overproduction of α-synuclein protein, followed by its aggregation and formation of amyloidogenic protein species, which differ in their size and structure and initiate death of nerve or glial cells. At present, better understanding of in vivo pathological processes requires studying behavioral effects of both the native α-synuclein protein and its individual amyloidogenic structures (oligomers and fibrils) obtained and characterized in vitro on animal models, as well as composite mixtures of these protein conformations. The aim of this work was to study effects of chronic nasal application of a composite mixture of native α-synuclein protein and α-synuclein oligomers on motor activity, short-term and long-term memory, and anxiety of aging mice. Methods. Experiments were carried out on 12-month old male C57Bl/6 mice, which received a solution of α-synuclein and its oligomers or a saline solution separately into each nostril for 14 days daily. Motor activity, short- and long-term memory and anxiety of animals were evaluated in Open Field, Novel Object Recognition, Conditioned Passive Avoidance, and Elevated Plus Maze tests. Results. The studied composite mixture of α-synuclein conformations did not induce statistically significant changes in behavioral indices of aging mice. At the same time, we have previously documented that in a similar experimental protocol, native α-synuclein initiates a decrease in motor activity, and α-synuclein oligomers - inhibition of motor activity and disorders of long-term memory and anxiety. Conclusion. The results indicated less pronounced behavioral effects of the composite mixture of native and oligomeric forms of α-synuclein compared with its individual components. The authors discussed possible mechanisms of the behavioral effects of the studied composite mixture of α-synuclein confirmations.


Author(s):  
James S.H. Wong ◽  
Catharine H. Rankin

The nematode, Caenorhabditis elegans (C. elegans), is an organism useful for the study of learning and memory at the molecular, cellular, neural circuitry, and behavioral levels. Its genetic tractability, transparency, connectome, and accessibility for in vivo cellular and molecular analyses are a few of the characteristics that make the organism such a powerful system for investigating mechanisms of learning and memory. It is able to learn and remember across many sensory modalities, including mechanosensation, chemosensation, thermosensation, oxygen sensing, and carbon dioxide sensing. C. elegans habituates to mechanosensory stimuli, and shows short-, intermediate-, and long-term memory, and context conditioning for mechanosensory habituation. The organism also displays chemotaxis to various chemicals, such as diacetyl and sodium chloride. This behavior is associated with several forms of learning, including state-dependent learning, classical conditioning, and aversive learning. C. elegans also shows thermotactic learning in which it learns to associate a particular temperature with the presence or absence of food. In addition, both oxygen preference and carbon dioxide avoidance in C. elegans can be altered by experience, indicating that they have memory for the oxygen or carbon dioxide environment they were reared in. Many of the genes found to underlie learning and memory in C. elegans are homologous to genes involved in learning and memory in mammals; two examples are crh-1, which is the C. elegans homolog of the cAMP response element-binding protein (CREB), and glr-1, which encodes an AMPA glutamate receptor subunit. Both of these genes are involved in long-term memory for tap habituation, context conditioning in tap habituation, and chemosensory classical conditioning. C. elegans offers the advantage of having a very small nervous system (302 neurons), thus it is possible to understand what these conserved genes are doing at the level of single identified neurons. As many mechanisms of learning and memory in C. elegans appear to be similar in more complex organisms including humans, research with C. elegans aids our ever-growing understanding of the fundamental mechanisms of learning and memory across the animal kingdom.


2020 ◽  
Vol 66 (2) ◽  
pp. 130-137
Author(s):  
B.A. Reikhardt ◽  
P.D. Shabanov

Protein kinase CK2 is an important enzyme in the nervous system. The nuclear forms of CK2 regulate chromatin structure and gene expression, the key processes for long-term memory formation. Memory modulators, the Structural Analogues of Etimizole (SAE), were able to increase or decrease the activity of chromatin-associated CK in the cortex and hippocampus of rat brain in vitro. In vivo memory enhancers from SAE-group (3 mg/kg) stimulated CK2 activity and the transcriptional ability of chromatin in the cortex and hippocampus, starting from 30 min with a peak for 60 min and a duration up to 180 min. At these periods the memory inhibitor from the SAE-group reduced CK2 activity and chromatin transcription. It is assumed that the modulating effect of SAE on CK2 activity and transcription underlies the effects of these compounds on long-term memory.


2020 ◽  
Vol 10 (2) ◽  
pp. 202-207
Author(s):  
Kanala Somasekhar Reddy ◽  
Pamisetty Likithasree ◽  
Ramlingam Peraman ◽  
Mallela Vijaya Jyothi ◽  
Chilamakuru Naresh Babu ◽  
...  

2015 ◽  
Vol 118 ◽  
pp. 80-88 ◽  
Author(s):  
Jiabin Zhang ◽  
Anne K. Tanenhaus ◽  
John C. Davis ◽  
Bret M. Hanlon ◽  
Jerry C.P. Yin

2011 ◽  
Vol 61 (2) ◽  
pp. 203-214 ◽  
Author(s):  
Jang-June Park ◽  
Sudarshan Anand ◽  
Yuming Zhao ◽  
Yumiko Matsumura ◽  
Yukimi Sakoda ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 828
Author(s):  
Elisa García-Lara ◽  
Samuel Aguirre ◽  
Núria Clotet ◽  
Xenia Sawkulycz ◽  
Clara Bartra ◽  
...  

Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer’s disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk.


PLoS Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. e3001062
Author(s):  
Diego Barriales ◽  
Itziar Martín-Ruiz ◽  
Ana Carreras-González ◽  
Marta Montesinos-Robledo ◽  
Mikel Azkargorta ◽  
...  

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.


2019 ◽  
Vol 5 (11) ◽  
pp. eaax3432 ◽  
Author(s):  
L. Scheunemann ◽  
A. Lampin-Saint-Amaux ◽  
J. Schor ◽  
T. Preat

Can mating influence cognitive functions such as learning and memory in a permanent way? We have addressed this question using a combined behavioral and in vivo imaging approach, finding that aversive long-term memory performance strongly increases in Drosophila females in response to sperm transfer following mating. A peptide in the male sperm, the sex peptide, is known to cause marked changes in female reproductive behavior, as well as other behaviors such as dietary preference. Here, we demonstrate that this sex peptide enhances memory by acting on a single pair of serotonergic brain neurons, in which activation of the sex peptide receptor stimulates the cyclic adenosine monophosphate/protein kinase A pathway. We thus reveal a strong effect of mating on memory via the neuromodulatory action of a sperm peptide on the female brain.


2008 ◽  
Vol 100 (1) ◽  
pp. 2-7 ◽  
Author(s):  
Donald A. Wilson ◽  
Christiane Linster

Habituation is one of the simplest forms of memory, yet its neurobiological mechanisms remain largely unknown in mammalian systems. This review summarizes recent multidisciplinary analyses of the neurobiology of mammalian odor habituation including in vitro and in vivo synaptic physiology, sensory physiology, behavioral pharmacology, and computational modeling approaches. The findings show that a metabotropic glutamate receptor–mediated depression of afferent synapses to the olfactory cortex is necessary and perhaps sufficient to account for cortical sensory adaptation and short-term behavioral habituation. Furthermore, long-term habituation is an N-methyl-d-aspartate (NMDA) receptor–dependent process within the olfactory bulb. Thus there is both a pharmacological and anatomical distinction between short-term and long-term memory for habituation. The differential locus of change underlying short- and long-term memory leads to predictable differences in their behavioral characteristics, such as specificity.


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