Semaphorin4A Is Cytotoxic to Oligodendrocytes and Is Elevated in Microglia and Multiple Sclerosis
In this study, we demonstrate that Sema4A is cytotoxic to OLs in culture: an effect accompanied by process collapse, membrane blebbing, and phosphatidylserine inversion. We further demonstrate that Sema4A preferentially binds to primary OLs but not astrocytes: an observation consistent with the lack of expression of Tim2 on astrocytes. We found that Sema4A protein levels are increased within multiple sclerosis plaques compared with normal-appearing white matter and that Sema4A induces lactate dehydrogenase release in a human OL cell line. The chief cellular source of Sema4A within the multiple sclerosis plaques appears to ...
Source: ASN Neuro - May 29, 2015 Category: Neuroscience Authors: Leitner, D. F., Todorich, B., Zhang, X., Connor, J. R. Tags: Original Article Source Type: research
ROS Produced by NOX2 Controls In Vitro Development of Cerebellar Granule Neurons Development
In this study, we evaluated the mechanisms by which ROS are regulated during neuronal development and the implications of these molecules in this process. Primary cultures of cerebellar granule neurons (CGN) were used to address these issues. Our results show that during the first 3 days of CGN development in vitro (days in vitro; DIV), the levels of ROS increased, reaching a peak at 2 and 3 DIV under depolarizing (25 mM KCl) and nondepolarizing (5 mM KCl) conditions. Subsequently, under depolarizing conditions, the ROS levels markedly decreased, but in nondepolarizing conditions, the ROS levels increased gradually. This c...
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Olguin-Albuerne, M., Moran, J. Tags: Original Article Source Type: research
Divergence in Endothelin-1- and Bradykinin-Activated Store-Operated Calcium Entry in Afferent Sensory Neurons
Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal through Gαq/11-protein coupled receptors (GPCRs) to produce nociceptor sensitization and pain. Both peptides activate phospholipase C to stimulate Ca2+ accumulation, diacylglycerol production, and protein kinase C activation and are rapidly desensitized via a G-protein receptor kinase 2-dependent mechanism. However, ET-1 produces a greater response and longer lasting nocifensive behavior than BK in multiple models, indicating a potentially divergent signaling mechanism in primary afferent sensory neurons. Using cultured sensory neurons, we de...
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Szteyn, K., Gomez, R., Berg, K. A., Jeske, N. A. Tags: Original Article Source Type: research
Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery
This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke. (Source: ASN Neuro)
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Leclerc, J. L., Lampert, A. S., Diller, M. A., Immergluck, J. B., Dore, S. Tags: Original Article Source Type: research
ROS Produced by NOX2 Control In Vitro Development of Cerebellar Granule Neurons Development
In this study, we evaluated the mechanisms by which ROS are regulated during neuronal development and the implications of these molecules in this process. Primary cultures of cerebellar granule neurons (CGN) were used to address these issues. Our results show that during the first 3 days of CGN development in vitro (days in vitro; DIV), the levels of ROS increased, reaching a peak at 2 and 3 DIV under depolarizing (25 mM KCl) and nondepolarizing (5 mM KCl) conditions. Subsequently, under depolarizing conditions, the ROS levels markedly decreased, but in nondepolarizing conditions, the ROS levels increased gradually. This c...
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Olguin-Albuerne, M., Moran, J. Tags: Original Article Source Type: research
Cystathionine {beta}-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury
Hydrogen sulfide (H2S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H2S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H2S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H2S...
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Chan, S. J., Chai, C., Lim, T. W., Yamamoto, M., Lo, E. H., Lai, M. K. P., Wong, P. T. H. Tags: Original Article Source Type: research
Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats
Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4–6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to...
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Chen, C., Shen, F.-Y., Zhao, X., Zhou, T., Xu, D.-J., Wang, Z.-R., Wang, Y.-W. Tags: Original Article Source Type: research
AAV-Mediated Gene Delivery in a Feline Model of Sandhoff Disease Corrects Lysosomal Storage in the Central Nervous System
This study demonstrates the therapeutic potential of AAV for feline SD and suggests a similar potential for human SD patients. (Source: ASN Neuro)
Source: ASN Neuro - April 13, 2015 Category: Neuroscience Authors: Rockwell, H. E., McCurdy, V. J., Eaton, S. C., Wilson, D. U., Johnson, A. K., Randle, A. N., Bradbury, A. M., Gray-Edwards, H. L., Baker, H. J., Hudson, J. A., Cox, N. R., Sena-Esteves, M., Seyfried, T. N., Martin, D. R. Tags: Original Article Source Type: research
Hypocalcemia-Induced Seizure: Demystifying the Calcium Paradox
Calcium is essential for both neurotransmitter release and muscle contraction. Given these important physiological processes, it seems reasonable to assume that hypocalcemia may lead to reduced neuromuscular excitability. Counterintuitively, however, clinical observation has frequently documented hypocalcemia’s role in induction of seizures and general excitability processes such as tetany, Chvostek’s sign, and bronchospasm. The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum. Nevertheless, several studies primarily addressing other biophy...
Source: ASN Neuro - March 24, 2015 Category: Neuroscience Authors: Han, P., Trinidad, B. J., Shi, J. Tags: Review Article Source Type: research
Caspase-Mediated Apoptosis in the Cochleae Contributes to the Early Onset of Hearing Loss in A/J Mice
In conclusion, our results suggest that caspase-mediated apoptosis in the cochleae, which may be related to a Cs mutation, contributes to the early onset of hearing loss in A/J mice. (Source: ASN Neuro)
Source: ASN Neuro - March 2, 2015 Category: Neuroscience Authors: Han, X., Ge, R., Xie, G., Li, P., Zhao, X., Gao, L., Zhang, H., Wang, O., Huang, F., Han, F. Tags: Original Article Source Type: research
Antitumor Activity of a Polypyridyl Chelating Ligand: In Vitro and In Vivo Inhibition of Glioma
Glioblastoma multiforme is an extremely aggressive and invasive form of central nervous system tumor commonly treated with the chemotherapeutic drug Temozolomide. Unfortunately, even with treatment, the median survival time is less than 12 months. 2,9-Di-sec-butyl-1,10-phenanthroline (SBP), a phenanthroline-based ligand originally developed to deliver gold-based anticancer drugs, has recently been shown to have significant antitumor activity in its own right. SBP is hypothesized to initiate tumor cell death via interaction with non-DNA targets, and considering most glioblastoma drugs kill tumors through DNA damage processe...
Source: ASN Neuro - March 2, 2015 Category: Neuroscience Authors: David, C. N., Frias, E. S., Elix, C. C., McGovern, K. E., Walker, A. M., Eichler, J. F., Wilson, E. H. Tags: Original Article Source Type: research
Identifying the Threshold of Iron Deficiency in the Central Nervous System of the Rat by the Auditory Brainstem Response
The deleterious effects of anemia on auditory nerve (AN) development have been well investigated; however, we have previously reported that significant functional consequences in the auditory brainstem response (ABR) can also occur as a consequence of marginal iron deficiency (ID). As the ABR has widespread clinical use, we evaluated the ability of this electrophysiological method to characterize the threshold of tissue ID in rats by examining the relationship between markers of tissue ID and severity of ABR latency defects. To generate various levels of ID, female Long-Evans rats were exposed to diets containing sufficien...
Source: ASN Neuro - March 2, 2015 Category: Neuroscience Authors: Greminger, A. R., Mayer-Proschel, M. Tags: Original Article Source Type: research
Control of Human PLP1 Expression Through Transcriptional Regulatory Elements and Alternatively Spliced Exons in Intron 1
Although the myelin proteolipid protein gene (PLP1) encodes the most abundant protein in central nervous system (CNS) myelin, not much is known about the mechanisms that govern expression of the human gene (hPLP1). Much more is known about the processes that regulate Plp1 gene expression in rodents. From studies with Plp1-lacZ transgenic mice, it was determined that the first intron of mouse Plp1 (mPlp1) is required to attain high levels of expression in brain, concurrent with the active myelination period. Other studies have suggested that within mPlp1 intron 1 (>8 kb) lie several regions with enhancer-like activity. T...
Source: ASN Neuro - February 18, 2015 Category: Neuroscience Authors: Hamdan, H., Kockara, N. T., Jolly, L. A., Haun, S., Wight, P. A. Tags: Original Article Source Type: research
Inducible HSP70 Is Critical in Preventing the Aggregation and Enhancing the Processing of PMP22
In this study, we show that activation of the chaperone pathway in fibroblasts from PMP22 duplication-associated Charcot–Marie–Tooth disease type 1A patient with an FDA-approved small molecule increases HSP70 expression and attenuates proteasome dysfunction. Using cells from an HSP70.1/3–/– (inducible HSP70) mouse model, we demonstrate that under proteotoxic stress, this chaperone is critical in preventing the aggregation of PMP22, and this effect is aided by macroautophagy. When examined at steady-state, HSP70 appears to play a minor role in the trafficking of wild-type-PMP22, while it is crucial f...
Source: ASN Neuro - February 18, 2015 Category: Neuroscience Authors: Chittoor-Vinod, V. G., Lee, S., Judge, S. M., Notterpek, L. Tags: Original Article Source Type: research
A Single-Nucleotide Polymorphism in Serine-Threonine Kinase 11, the Gene Encoding Liver Kinase B1, Is a Risk Factor for Multiple Sclerosis
We identified a family in which five siblings were diagnosed with multiple sclerosis (MS) or clinically isolated syndrome. Several women in the maternal lineage have comorbidities typically associated with Peutz Jeghers Syndrome, a rare autosomal-dominant disease caused by mutations in the serine-threonine-kinase 11 (STK11) gene, which encodes liver kinase B1. Sequence analysis of DNA from one sibling identified a single-nucleotide polymorphism (SNP) within STK11 intron 5. This SNP (dbSNP ID: rs9282860) was identified by TaqMan polymerase chain reaction (PCR) assays in DNA samples available from two other siblings. Further...
Source: ASN Neuro - February 18, 2015 Category: Neuroscience Authors: Boullerne, A. I., Skias, D., Hartman, E. M., Testai, F. D., Kalinin, S., Polak, P. E., Feinstein, D. L. Tags: Original Article Source Type: research
