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Given the recent findings on the importance of CD38 signaling in the pathogenesis of colon cancer. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in colon cancer patients accounts for some of the clinical heterogeneity. CD38 is considered a marker of prognosis and as an indicator the activation and proliferation of cells. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. We evaluated one potentially functional CD38 SNP, intronic rs6449182 in two cases patients and controls. Genotyping was done using PCR-based assays in a total of 93 patients with colon cancer and 100 controls. We found that frequencies of variant allele (rs6449182 G) were significantly higher in colon cancer. Logistic regression analysis revealed an association between colon cancer and genotypes: rs6449182 CC [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.32 – 1.01], rs6449182 CG (OR, 1.47; 95% CI, 0.83 – 2.60), and rs6449182 GG (OR, 2.26; 95% CI, 0.66 – 7.77). We observed that rs6449182 G carriers had more advanced clinical stage (P = 0.04). In conclusion, our data show that CD38 SNP may affect CD38 expression and contribute to the increased risk of colon cancer carcinogenesis.

Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis. 

The presynaptic modifications that accompany long-term changes in synaptic plasticity are still not fully understood. Synaptophysin is a major synaptic vesicle protein involved in neurotransmitter release. We have used quantitative electron microscopy to study synaptophysin (Syn) immunolabelling in the hippocampus of adult rats 24h after induction in vivo of long term potentiation (LTP), and long term depression (LTD). Electrodes were implanted chronically in hippocampus with stimulation at either the medial (MPP) or lateral perforant path (LPP). 24h following induction of LTP or LTD rats were rapidly perfusion fixed and hippocampal tissue processed to electron microscopy via freeze substitution method. Anti-synaptophysin post-embedding immunolabelling was performed and tissue was imaged in the middle molecular layer (MML) of the dentate gyrus. There was a significant decrease in number of Syn labelled vesicles per unit area of bouton after LTP, but not LTD. An analysis of the spatial distribution of Syn labelled synaptic vesicles showed an increase in nearest neighbour distances, more so in the LTP than the LTD group, which is consistent with the overall decrease of Syn after LTP. These data are in agreement with the suggestion that Syn is involved in clathrin-dependent and “kiss and run” endocytosis which occurs perisynaptically. Thus, an increase in release of neurotransmitter and in consequence endocytosis would be consistent with an increased active zone distance for vesicles containing Syn.

We revisit the Wendling-Chauvel neural mass model by reducing it to eight ODEs and adding a dierential equation that accounts for a dynamic evolution of the slow inhibitory synaptic gain. This allows to generate dynamic transitions in the resulting nine-dimensional model. The output of the extended model can be related to EEG patterns observed during epileptic seizure, in particular isolated pre-ictal spikes and low-voltage fast oscillations at seizure onset. We analyse the extended model using basic tools from slow-fast dynamical systems theory and relate the main transitions towards seizure states to torus canards, a type of solutions that has been shown to explain the spiking to bursting transition in many neural models. We nd that the original ten-dimensional Wendling-Chauvel model can be reduced to eight dimensions, two variables being scaled versions of two other variables of the model. We then obtain a model with four PSP blocks, which is consistent with the block-diagrams typically presented to describe this model. Instead of varying the slow inhibitory synaptic gain parameter B quasi-statically, or just performing numerical bifurcation analysis in B as the structure of the fast subsystem of an hypothetical extended system, we construct a true slow dynamics for B, depending sensitively on the main PSP output of the model, Y0. Near fold bifurcation of limit cycles of the original model, the solution to the extended model performs fast low-amplitude oscillations close to both attracting and repelling branches of limit cycles, which is the signature of a torus canard phenomenon.

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.

Thyroid hormones (THs) are essential for the development and function of the central nervous system (CNS), not only for neuronal cells but also for glial development and differentiation. In adult CNS, both hypo- and hyper-thyroidism may affect psychological condition and potentially increase the risk of cognitive impairment and neurodegeneration including Alzheimer’s disease (AD). We have reported non-genomic effects of tri-iodothyronine (T3) on microglial functions and its signaling in vitro (MORI et al., 2015). Here we report the effects of hyperthyroidism on glial cells in vivo using young and old male and female mice. Immunohistochemical analyses showed glial activation are sex- and age-dependent. We also injected fluorescent-labeled amyloid β peptide (Aβ1-42) intracranially to L-thyroxine (T4)–injected hyperthyroid model mice and observed sex-dependent microglial phagocytosis in vivo as well. These results may partly explain the gender- and age-dependent differences in neurological and psychological symptoms of thyroid dysfunction.