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Understanding the molecular and cellular processes that cause dementia is one of the most important challenges in neuroscience. SUMOylation is a post-translational protein modification that has been strongly implicated in neurodegenerative diseases. To investigate SUMOylation in dementia we profiled the expression of key SUMOylation pathway proteins in post mortem brain tissue from Alzheimer’s Disease (AD) and Down’s Syndrome (DS) patients. As expected, both AD and DS tissue displayed massively increased levels of phosphorylated tau compared to age- and sex-matched controls. Surprisingly, there were no changes in the levels of the E1 and E2 enzymes required for protein SUMOylation, or in levels of the deSUMOylating enzyme SENP1.  There was, however, a marked decrease in the SUMO-2/3-specific deSUMOylating enzyme SENP3 in DS. There were also increased levels of SUMO-1 conjugated proteins in DS, but not in AD tissue. While these results do not exclude roles for SUMOylation in AD, they demonstrate clear differences in the profile of SUMOylation and in the expression of deSUMOylating enzymes between AD and DS brain.

The assembly of neural circuits during development endows the brain with the ability to perceive the environment, control motor output, and perform higher cognitive functions. Failure to assemble proper neural circuits may result in neurodevelopmental disorders including intellectual disability and autism spectrum disorders. Epigenetic mechanisms, and in particular chromatin remodeling, are potent regulators of neuronal connectivity. Here, we review recent studies highlighting the essential role of the ATPdependent nucleosomal remodeling and deacetylase (NuRD) complex in epigenetic programming of neurons to drive neural circuit assembly and organism behavior. 

Neurons adapt to stimuli through activity dependent changes to their transcriptome, a process mediated by immediate-early gene networks.  Recent findings that transcriptional activation of neuronal immediate-early genes requires the formation of controlled DNA double-strand breaks (DSBs) has come as a surprise and has profound implications for neuronal function, especially in the aging brain.  Here we review recent literature surrounding the phenomena of activity-dependent DNA DSBs in neurons and how this process may be exploited by transposable elements (TEs) in both naïve and aging neurons.  We hypothesize the existence of Activity DEPendent Transposition (ADEPT), where neuronal excitation is able to induce genomic rearrangements through either de novo integration of TEs or by homology-directed recombination of TE-derived repetitive sequences.  Epigenetic drift may cause the magnitude of ADEPT to increase with age, leading to genome instability, which we suggest presages most, if not all, neurodegenerative diseases.

Neural prostheses (NPs) link the brain to external devices, with an eventual goal of recovery of motor and sensory functions to patients with neurological conditions. Over the past half-century, NPs have advanced significantly from the early ideas that sounded like science fiction to the modern high-tech implementations. In particular, invasive recordings using multichannel implants have enabled real-time control of artificial limbs by nonhuman primates and human subjects. Furthermore, NPs can provide artificial sensory feedback, allowing users to perceive the movements of prosthetic limbs and their haptic interaction with external objects. Recently, NP approach was used to build brain-nets that enable information exchange between individual brains and execution of cooperative tasks. This review focuses on invasive NPs for sensorimotor functions.

Matrix metalloproteinase 9, MMP-9 is an extracellularly operating enzyme that has been demonstrated as an important regulatory molecule in control of synaptic plasticity, learning and memory. Either genetic or pharmacological inhibition of MMP-9 impairs late phase of long-term potentiation at various pathways, as well as appetitive and spatial memory formation, although aversive learning remains apparently intact in MMP-9 KO mice. MMP-9 is locally translated and released from the excitatory synapses in response to neuronal activity. Extrasynaptic MMP-9 is required for growth and maturation of the dendritic spines to accumulate and immobilize AMPA receptors, making the excitatory synapses more efficacious. Animal studies have implicated MMP-9 in such neuropsychiatric conditions, as e.g., epileptogenesis, autism spectrum disorders, development of addiction, and depression. In humans, MMP-9 appears to contribute to epilepsy, alcohol addiction, Fragile X Syndrome, schizophrenia and bipolar disorder. In aggregate, all those conditions may be considered as relying on alterations of dendritic spines/excitatory synapses and thus understanding the role played by MMP-9 in the synaptic plasticity may allow to elucidate the underpinnings of major neuropsychiatric disorders.

This review focuses on general optogenetics issues (in particular the choice of the necessary light exposure settings), as well as certain promising areas of research with optogenetics.

Maintenance of genome stability in the face of DNA damage is essential for cellular homeostasis and prevention of cancer and brain degeneration. The DNA damage response (DDR) is a complex response that is rapidly activated when a DNA lesion occurs in chromosomal DNA. Mutations affecting the proteins involved in the DDR can lead to genomic instability syndromes that involve tissue degeneration, cancer predisposition, premature aging, and brain mal-development and degeneration. Mutation of the kinase ATM leads to a prototype genomic instability syndrome, ataxia-telangiectasia (A-T). A-T is characterized by progressive cerebellar degeneration, immunodeficiency, genome instability, premature aging, gonadal dysgenesis, extreme radiosensitivity, and high incidence of lymphoreticular malignancies. One of the most devastating symptoms of A-T — cerebellar ataxia — develops progressively into general motor dysfunction. Based on our previous studies we hypothesized that the neurological deficits in genomic instability disorders stem (at least in part) from significant reduction in functionality of glial cells. We further hypothesized that impaired vascularization affects the environment in which the neurons and glial cells function, thereby reducing neuronal cell functionality. We found that ATM deficiency led to aberrant astrocytic morphology and alterations of vasculature both in cerebellum and the visual system. Moreover, we found reduced myelin basic protein immunoreactivity and signs of inflammation in ATM-deficient cerebella and optic nerve.  Interestingly, similar findings have been reported in patients with other genomic instability disorders. These observations bolster the notion that astrocyte-specific pathologies and hampered vascularization and astrocyte-neuron interactions in the CNS play crucial roles in the etiology of genome instability brain disorders and underlie brain degeneration at specific sites.

A conspicuous ability of the mammalian brain to integrate and process huge amount of spatial, visual and temporal stimuli is a result of its enormous structural complexity functioning in an integrated way as a whole. Here we review recent achievements in the understanding of brain structure and function. A traditional view on the brain as a network of neurons has been extended to the more complicated structure including overlapping and interacting networks of neurons and glial cells. We discuss artificial versus natural neural networks and consider a concept of attractor networks. Moreover, we speculate that each neuron can have an intracellular network on a genetic level, based and functioning on the principle of artificial intelligence. Hence, we speculate that mammalian brain is, in fact, a network of networks. We review different aspects of this structure and propose that the study of brain can be successful only if we utilize the concepts recently developed in nonlinear dynamics: the concept of integrated information, emergence of collective dynamics and taking account of unexpected behavior and regimes due to nonlinearity. Additionally, we discuss perspectives of medical applications to be developed following this research direction.

Classically, the central nervous system (CNS) was considered to contain neurons and three main types of glial cells - astrocytes, oligodendrocytes, and microglia.  Now, it has been clearly established that NG2-glia are a fourth glial cell type that are defined by their expression of the NG2 chondroitin sulfate proteoglycan (Cspg4).  NG2-glia are also known as oligodendrocyte precursor cells (OPCs) and express the alpha receptor for platelet-derived growth factor (Pdgfra) as well as other oligodendrocyte lineage markers. NG2-glia are most numerous during CNS development when they are responsible for massive generation of oligodendrocytes, the myelin-forming cells of the CNS. A significant population of NG2-glia persist in the adult CNS, where they generate oligodendrocytes throughout life. A unique feature of NG2-glia is that they receive synaptic inputs from neurons and are able to respond rapidly to neurotransmission via their specific ion channel and receptor profiles. Moreover, synaptic and neuronal integrity depend on NG2-glia. Notably, concomitant disruption of NG2-glia, myelin and neurotransmission are key features of many neuropathologies, including Multiple Sclerosis and Alzheimer’s disease (AD). The fact that neurotransmission both regulates and is reliant on NG2-glia and myelin raises the ‘chicken and egg’ question of what comes first – disruption of NG2-glia/myelin or synapses/neurons. It is more useful to think of neurons, NG2-glia and oligodendrocytes/myelin as being functionally integrated and interdependent units, whereby disruption of any one can result in a vicious cycle with potentially devastating effects on CNS function.

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The effect of 2-aminoethyl diphenylborinate (2-APB), a commonly used drug to modulate inositol-1,4,5-triphosphate (IP3) receptors and transient receptor potential (TRP) channels, on GABAA receptor-mediated currents was studied in neurons from the medial preoptic nucleus (MPN) of rat. 2-APB gradually and reversibly reduced the currents evoked by GABA but had no effect on the currents evoked by glycine. The blocking effect was not mediated by alterations in intracellular calcium concentration and showed a concentration dependence with half maximal effect at ~50 µM 2-APB, for currents evoked by 100 µM, as well as by 1.0 mM GABA, suggesting that 2-APB is not competing with GABA for its binding site at the GABAA receptor. Thus, the present study describes a novel pharmacological property of 2-APB as a non-competitive blocker of GABAA receptors and calls for caution in the interpretation of the results where 2-APB is used to affect IP3 receptors or TRP channels.

Stem cells research has passed a long and exciting way from the discovery to clinical applications. Every year more-and-more scientific reports and solid research breakthroughs are published in this fascinating field making it difficult to follow after new discoveries and cover the history. In the current review we overviewed history of stem cells research starting from the discovery and ending with the current state-of-art. We discussed obstacles and future perspectives of the cell-based therapy, with a special focus made on protection and regeneration of the lost functions after injury/degeneration of adult central nervous system.