scholarly journals Retrotransposon-induced mosaicism in the neural genome

Open Biology ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. 180074 ◽  
Author(s):  
Gabriela O. Bodea ◽  
Eleanor G. Z. McKelvey ◽  
Geoffrey J. Faulkner

Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to be transcribed and mobilized in the brain. Retrotransposition in the developing brain, as well as during adult neurogenesis, provides a milieu in which neural diversity can arise. Dysregulation of retrotransposon activity may also contribute to neurological disease. Here, we review recent reports of retrotransposon activity in the brain, and discuss the temporal nature of retrotransposition and its regulation in neural cells in response to stimuli. We also put forward hypotheses regarding the significance of retrotransposons for brain development and neurological function, and consider the potential implications of this phenomenon for neuropsychiatric and neurodegenerative conditions.

2020 ◽  
Vol 18 (6) ◽  
pp. 20-26
Author(s):  
O.K. Netrebenko ◽  

At present, the prevalence of mental disorders among children and adults is growing rapidly. For example, according to statistical data, the prevalence rates of all mental diseases in Russia have grown by 10 times during the past 45 years. Apparently, one of the causes might be impairment of the processes of normal programming of metabolic and brain function, which occurs during the critical period of the first 1000 days of life. Any imbalances in the environment and nutrition in that period might change the function of genes responsible for production of neurotransmitters, neurotrophic factors, and other molecules involved in synaptogenesis, dendritic synthesis. A factor influencing the brain development processes that is most accessible for modification is nutrition. Nutrition of a pregnant woman and baby, as well as the state of intestinal microbiota, influence the expression of genes important for an adequate brain development. Key words: nutrition, brain development, neuropsychological disorders


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1254 ◽  
Author(s):  
Amy J. Tibbo ◽  
George S. Baillie

Phosphodiesterases (PDEs) are the only superfamily of enzymes that have the ability to break down cyclic nucleotides and, as such, they have a pivotal role in neurological disease and brain development. PDEs have a modular structure that allows targeting of individual isoforms to discrete brain locations and it is often the location of a PDE that shapes its cellular function. Many of the eleven different families of PDEs have been associated with specific diseases. However, we evaluate the evidence, which suggests the activity from a sub-family of the PDE4 family, namely PDE4B, underpins a range of important functions in the brain that positions the PDE4B enzymes as a therapeutic target for a diverse collection of indications, such as, schizophrenia, neuroinflammation, and cognitive function.


2003 ◽  
Vol 23 (19) ◽  
pp. 6739-6749 ◽  
Author(s):  
Shuhei Tomita ◽  
Masaki Ueno ◽  
Masami Sakamoto ◽  
Yuki Kitahama ◽  
Masaaki Ueki ◽  
...  

ABSTRACT Hypoxia-inducible factor 1α (HIF-1α) is essential for vascular development during embryogenesis and pathogenesis. However, little is known about its role in brain development. To investigate the function of HIF-1α in the central nervous system, a conditional knockout mouse was made with the Cre/LoxP system with a nestin promoter-driven Cre. Neural cell-specific HIF-1α-deficient mice exhibit hydrocephalus accompanied by a reduction in neural cells and an impairment of spatial memory. Apoptosis of neural cells coincided with vascular regression in the telencephalon of mutant embryos, and these embryonic defects were successfully restored by in vivo gene delivery of HIF-1α to the embryos. These results showed that expression of HIF-1α in neural cells was essential for normal development of the brain and established a mouse model that would be useful for the evaluation of therapeutic strategies for ischemia, including hypoxia-mediated hydrocephalus.


2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.


2020 ◽  
Vol 20 (9) ◽  
pp. 800-811 ◽  
Author(s):  
Ferath Kherif ◽  
Sandrine Muller

In the past decades, neuroscientists and clinicians have collected a considerable amount of data and drastically increased our knowledge about the mapping of language in the brain. The emerging picture from the accumulated knowledge is that there are complex and combinatorial relationships between language functions and anatomical brain regions. Understanding the underlying principles of this complex mapping is of paramount importance for the identification of the brain signature of language and Neuro-Clinical signatures that explain language impairments and predict language recovery after stroke. We review recent attempts to addresses this question of language-brain mapping. We introduce the different concepts of mapping (from diffeomorphic one-to-one mapping to many-to-many mapping). We build those different forms of mapping to derive a theoretical framework where the current principles of brain architectures including redundancy, degeneracy, pluri-potentiality and bow-tie network are described.


Author(s):  
Sascha R. A. Alles ◽  
Anne-Marie Malfait ◽  
Richard J. Miller

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.


2021 ◽  
Vol 10 (11) ◽  
pp. 2358
Author(s):  
Maria Grazia Giovannini ◽  
Daniele Lana ◽  
Chiara Traini ◽  
Maria Giuliana Vannucchi

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.


2021 ◽  
Vol 22 (14) ◽  
pp. 7664
Author(s):  
Katarzyna Bartkowska ◽  
Krzysztof Turlejski ◽  
Beata Tepper ◽  
Leszek Rychlik ◽  
Peter Vogel ◽  
...  

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.


1995 ◽  
Vol 7 (1) ◽  
pp. 1-6 ◽  
Author(s):  
D.R.A. Uges

SummaryToxicology is one of the eldest areas of special attention in medicine and pharmacy. In the past, forensic toxicology was the most important part, but nowadays, at least in the Netherlands, the clinical, occupational and environmental toxicology have the centre of attention.The brain plays its own role in the clinical toxicology. There the intoxication can take place, it can be the basis of the peripheral symptoms of the intoxication or it can be the cause of the intoxication, e.g. at a suicidal attempt or the hospital addiction syndrome.The somatic treatment of an intoxicated patient includes in the first place the stabilization of the patient (cardio-vascular, ventilation and central effects); then the removal of the poison from the surroundings and out of the patient by different suitable methods and finally the symptomatic treatment, sometimes with antidotes.In the Netherlands, hardly any intoxication is fatal, when the patient arrives in the hospital in time, or euthanasia took place on purpose.


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