Hypothalamic Subependymal Niche: A Novel Site of the Adult Neurogenesis

The discovery of undifferentiated, actively proliferating neural stem cells (NSCs) in the mature brain opened a brand new chapter in the contemporary neuroscience. Adult neurogenesis appears to occur in specific brain regions (including hypothalamus) throughout vertebrates’ life, being considered an important player in the processes of memory, learning, and neural plasticity. In the adult mammalian brain, NSCs are located mainly in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the subventricular zone (SVZ) of the lateral ventricle ependymal wall. Besides these classical regions, hypothalamic neurogenesis occurring mainly along and beneath the third ventricle wall seems to be especially well documented. Neurogenic zones in SGZ, SVZ, and in the hypothalamus share some particular common features like similar cellular cytoarchitecture, vascularization pattern, and extracellular matrix properties. Hypothalamic neurogenic niche is formed mainly by four special types of radial glia-like tanycytes. They are characterized by distinct expression of some neural progenitor and stem cell markers. Moreover, there are numerous suggestions that newborn hypothalamic neurons have a significant ability to integrate into the local neural pathways and to play important physiological roles, especially in the energy balance regulation. Newly formed neurons in the hypothalamus can synthesize and release food intake regulating neuropeptides and they are sensitive to the leptin. On the other hand, high-fat diet positively influences hypothalamic neurogenesis in rodents. The nature of this intriguing new site of adult neurogenesis is still so far poorly studied and requires further investigations.     

Unsupervised Learning and Adaptation in a Model of Adult Neurogenesis

Adult neurogenesis has long been documented in the vertebrate brain and recently even in humans. Although it has been conjectured for many years that its functional role is related to the renewing of memories, no clear mechanism as to how this can be achieved has been proposed. Using the mammalian olfactory bulb as a paradigm, we present a scheme in which incorporation of new neurons proceeds at a constant rate, while their survival is activity-dependent and thus contingent on new neurons establishing suitable connections. We show that a simple mathematical model following these rules organizes its activity so as to maximize the difference between its responses and can adapt to changing environmental conditions in unsupervised fashion, in agreement with current neurophysiological data.     

Partial Purification of a Novel N-Ethylmaleimide-Activated Translational Inhibitor from Adult Rat Brain

A translational inhibitor that is activated by N-ethylmaleimide treatment can be found in the postmicrosomal fraction prepared from the brain of adult rats, but it is almost undetectable in the same fraction prepared from suckling animals. The inhibitor is thermolabile and remains in the supernatant fraction after precipitation at pH 5. During the purification procedure, the inhibitor in its unactivated state binds to the anion exchanger (diethylaminoethyl-cellulose) but not to the cation exchanger (phosphocellulose). Treatment with N-ethylmaleimide increases inhibitor affinity for the cation exchanger, and this chromatographic step purifies the inhibitor by 143-fold. Both the thermolabile nature and the behavior of the inhibitory activity during the different steps of the purification procedure suggest that this activity is most probably due to a protein. Although the addition of initiation factor 2 reverses the inhibition of protein synthesis in the presence of ATP and Mg2+, the inhibitor does not phosphorylate any of the initiation factor subunits "in vitro," which indicates that it does not contain any intrinsic protein kinase activity. However, its presence in both a crude and a purified preparation of a kinase of the alpha subunit of a brain eukaryotic initiation factor increases the phosphorylation of the alpha subunit of the initiation factor. The mechanism of action of this inhibitor is discussed.     

The Effects of Amiloride on Seizure Activity,Cognitive Deficits and Seizure-Induced Neurogenesis in a Novel Rat Model of Febrile Seizures

Neurochemical Research - Accumulating data suggest that sodium–hydrogen exchangers (NHEs) play a key role in modulating seizure activity by regulating neuronal pH in the brain. Amiloride, an...     

Photochemical Damage in the Albino Rat Retina: Oral Taurine Has No Effect on DNA and Protein Loss from Severely Damaged Photoreceptor Cells

Albino Wistar rats were exposed continuously to fluorescent light, causing photoreceptor destruction over a period of 4 days. The rate of DNA and protein loss from the cells was not affected by administration of 5% taurine in the drinking water.     

The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.     

Spatial and Temporal Attention Modulate the Early Stages of Face Processing: Behavioural Evidence from a Reaching Paradigm

A presently unresolved question within the face perception literature is whether attending to the location of a face modulates face processing (i.e. spatial attention). Opinions on this matter diverge along methodological lines – where neuroimaging studies have observed that the allocation of spatial attention serves to enhance the neural response to a face, findings from behavioural paradigms suggest face processing is carried out independently of spatial attention. In the present study, we reconcile this divide by using a continuous behavioural response measure that indexes face processing at a temporal resolution not available in discrete behavioural measures (e.g. button press). Using reaching trajectories as our response measure, we observed that although participants were able to process faces both when attended and unattended (as others have found), face processing was not impervious to attentional modulation. Attending to the face conferred clear benefits on sex-classification processes at less than 350ms of stimulus processing time. These findings constitute the first reliable demonstration of the modulatory effects of both spatial and temporal attention on face processing within a behavioural paradigm.     

Serotonin Inhibits Acetylcholine Release from Rat Striatum Slices: Evidence for a Presynaptic Receptor-Mediated Effect

Rat brain striatum slices were incubated with [3H]choline, perfused with a physiological buffer, and stimulated by perfusion with a K+-enriched buffer for 2 min. The tritium overflow evoked by K+ was decreased by 5-hydroxytryptamine (serotonin, 5-HT) (maximal inhibition 10(-6) M). This effect of 5-HT was mimicked by several agonists (5-methoxytryptamine, N,N-dimethyl-tryptamine, bufotenin) and blocked by serotonergic antagonists (methiothepin, methysergide, cinanserin) but not by haloperidol; methiothepin and methysergide alone slightly increased the K+-evoked overflow of tritium (3H). Inhibition of the tritium release by 5-HT was not suppressed in the presence of tetrodotoxin (TTX) (10(-6) M). These results suggest that 5-HT tonically inhibits acetylcholine (ACh) release from striatal cholinergic neurons by acting on a presynaptic receptor localized on cholinergic terminals.     

Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo

Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po₂ values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po₂ levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.     

Male-Specific Differences in Proliferation,Neurogenesis, and Sensitivity to Oxidative Stress in Neural Progenitor Cells Derived from a Rat Model of ALS

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor dysfunction and the loss of large motor neurons in the spinal cord and brain stem. A clear genetic link to point mutations in the superoxide dismutase 1 (SOD1) gene has been shown in a small group of familial ALS patients. The exact etiology of ALS is still uncertain, but males have consistently been shown to be at a higher risk for the disease than females. Here we present male-specific effects of the mutant SOD1 transgene on proliferation, neurogenesis, and sensitivity to oxidative stress in rat neural progenitor cells (rNPCs). E14 pups were bred using SOD1^G93A transgenic male rats and wild-type female rats. The spinal cord and cortex tissues were collected, genotyped by PCR using primers for the SOD1^G93A transgene or the male-specific Sry gene, and cultured as neurospheres. The number of dividing cells was higher in male rNPCs compared to female rNPCs. However, SOD1^G93A over-expression significantly reduced cell proliferation in male cells but not female cells. Similarly, male rNPCs produced more neurons compared to female rNPCs, but SOD1^G93A over-expression significantly reduced the number of neurons produced in male cells. Finally we asked whether sex and SOD1^G93A transgenes affected sensitivity to oxidative stress. There was no sex-based difference in cell viability after treatment with hydrogen peroxide or 3-morpholinosydnonimine, a free radical-generating agent. However, increased cytotoxicity by SOD1^G93A over-expression occurred, especially in male rNPCs. These results provide essential information on how the mutant SOD1 gene and sexual dimorphism are involved in ALS disease progression.     

Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background

Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer''s disease.

Methodology/Principal Findings

To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased.

Conclusions/Significance

We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.     

No Chemopreventive Effect of Nonsteroidal Anti-Inflammatory Drugs on Nonmelanoma Skin Cancer: Evidence from Meta-Analysis

Background

Nonmelanoma skin cancer (NMSC),which includes squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is the most common form of cancer, and its incidence is increasing. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to be chemopreventive for NMSC. However, the results from published studies were controversial.

Methods

We searched the PubMed and Embase databases for relevant studies. Moreover, relevant reviews regarding the use of NSAIDs for NMSC patients were examined for potential inclusive studies. To measure the effects of NSAIDs, the relative risk (RR) was analyzed.

Results

A Total of 8 studies were included in our meta-analysis. We found that NSAIDs use was not associated with a reduced risk of SCC or BCC under the random effects model (pooled RR  =  0.86, 95% CI, 0.73–1.02, P  =  0.085; pooled RR  =  0.94, 95% CI 0.85–1.04, P  =  0.266; respectively).

Conclusion

From the included studies, we found no statistically significant chemopreventive effect on NMSC of NSAIDs. This finding warrants more prospective studies evaluating the relationship between NSAIDs and NMSC.     

The Brain Ages Optimally to Model Its Environment: Evidence from Sensory Learning over the Adult Lifespan

The aging brain shows a progressive loss of neuropil, which is accompanied by subtle changes in neuronal plasticity, sensory learning and memory. Neurophysiologically, aging attenuates evoked responses—including the mismatch negativity (MMN). This is accompanied by a shift in cortical responsivity from sensory (posterior) regions to executive (anterior) regions, which has been interpreted as a compensatory response for cognitive decline. Theoretical neurobiology offers a simpler explanation for all of these effects—from a Bayesian perspective, as the brain is progressively optimized to model its world, its complexity will decrease. A corollary of this complexity reduction is an attenuation of Bayesian updating or sensory learning. Here we confirmed this hypothesis using magnetoencephalographic recordings of the mismatch negativity elicited in a large cohort of human subjects, in their third to ninth decade. Employing dynamic causal modeling to assay the synaptic mechanisms underlying these non-invasive recordings, we found a selective age-related attenuation of synaptic connectivity changes that underpin rapid sensory learning. In contrast, baseline synaptic connectivity strengths were consistently strong over the decades. Our findings suggest that the lifetime accrual of sensory experience optimizes functional brain architectures to enable efficient and generalizable predictions of the world.     

Effect of Calcitonin Gene-Related Peptide on the Neurogenesis of Rat Adipose-Derived Stem Cells In Vitro

Calcitonin gene-related peptide (CGRP) promotes neuron recruitment and neurogenic activity. However, no evidence suggests that CGRP affects the ability of stem cells to differentiate toward neurogenesis. In this study, we genetically modified rat adipose-derived stem cells (ADSCs) with the CGRP gene (CGRP-ADSCs) and subsequently cultured in complete neural-induced medium. The formation of neurospheres, cellular morphology, and proliferative capacity of ADSCs were observed. In addition, the expression of the anti-apoptotic protein Bcl-2 and special markers of neural cells, such as Nestin, MAP2, RIP and GFAP, were evaluated using Western blot and immunocytochemistry analysis. The CGRP-ADSCs displayed a greater proliferation than un-transduced (ADSCs) and Vector-transduced (Vector-ADSCs) ADSCs (p<0.05), and lower rates of apoptosis, associated with the incremental expression of Bcl-2, were also observed for CGRP-ADSCs. Moreover, upon neural induction, CGRP-ADSCs formed markedly more and larger neurospheres and showed round cell bodies with more branching extensions contacted with neighboring cells widely. Furthermore, the expression levels of Nestin, MAP2, and RIP in CGRP-ADSCs were markedly increased, resulting in higher levels than the other groups (p<0.05); however, GFAP was distinctly undetectable until day 7, when slight GFAP expression was detected among all groups. Wnt signals, primarily Wnt 3a, Wnt 5a and β-catenin, regulate the neural differentiation of ADSCs, and CGRP gene expression apparently depends on canonical Wnt signals to promote the neurogenesis of ADSCs. Consequently, ADSCs genetically modified with CGRP exhibit stronger potential for differentiation and neurogenesis in vitro, potentially reflecting the usefulness of ADSCs as seed cells in therapeutic strategies for spinal cord injury.     

Neurogenesis in the Diseased Adult Human Brain: New Therapeutic Strategies for Neurodegenerative Diseases

No abstract available.     

Macroalgae Has No Effect on the Severity and Dynamics of Caribbean Yellow Band Disease

By removing herbivores and promoting increases in macroalgae, overfishing is thought to indirectly cause coral disease and mortality. We performed three field manipulations to test the general hypothesis that overfishing and the subsequent alteration of coral reef trophic dynamics are a cause of coral epizootics. Specifically, we asked whether the presence of macroalgae can influence within- and among-colony spread rates of Caribbean Yellow Band Disease in Montastraea faveolata. Macroalgae were placed next to infected and healthy, adult and small coral colonies to measure effects on disease spread rate, coral growth and coral survival. Surprisingly, the addition of macroalgae did not affect disease severity or coral fitness. Our results indicate that macroalgae have no effect on the severity and dynamics of Caribbean Yellow Band Disease and that fisheries management alone will not mitigate the effects of this important epizootic.     

Streptomycin Application Has No Detectable Effect on Bacterial Community Structure in Apple Orchard Soil

Streptomycin is commonly used to control fire blight disease on apple trees. Although the practice has incited controversy, little is known about its nontarget effects in the environment. We investigated the impact of aerial application of streptomycin on nontarget bacterial communities in soil beneath streptomycin-treated and untreated trees in a commercial apple orchard. Soil samples were collected in two consecutive years at 4 or 10 days before spraying streptomycin and 8 or 9 days after the final spray. Three sources of microbial DNA were profiled using tag-pyrosequencing of 16S rRNA genes: uncultured bacteria from the soil (culture independent) and bacteria cultured on unamended or streptomycin-amended (15 μg/ml) media. Multivariate tests for differences in community structure, Shannon diversity, and Pielou''s evenness test results showed no evidence of community response to streptomycin. The results indicate that use of streptomycin for disease management has minimal, if any, immediate effect on apple orchard soil bacterial communities. This study contributes to the profile of an agroecosystem in which antibiotic use for disease prevention appears to have minimal consequences for nontarget bacteria.     

Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of Diabetes

Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p<0.05). Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p<0.05). The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p<0.05), and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p<0.05). In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.