NeurosignalsPub Date : 2012-01-01Epub Date: 2012-01-18DOI: 10.1159/000331899
Keri Man Chi Mak, Amy Cheuk Yin Lo, Amy Ka Man Lam, Patrick Ka Kit Yeung, Ben Chi Bun Ko, Stephen Sum Man Chung, Sookja Kim Chung
{"title":"Nuclear factor of activated T cells 5 deficiency increases the severity of neuronal cell death in ischemic injury.","authors":"Keri Man Chi Mak, Amy Cheuk Yin Lo, Amy Ka Man Lam, Patrick Ka Kit Yeung, Ben Chi Bun Ko, Stephen Sum Man Chung, Sookja Kim Chung","doi":"10.1159/000331899","DOIUrl":"https://doi.org/10.1159/000331899","url":null,"abstract":"<p><p>Nuclear factor of activated T cells 5 (NFAT5) has been implicated in regulating several genes that are thought to be neuroprotective in ischemic injury. Because of the embryonic lethality of NFAT5 knockout (NFAT5(-/-)) mice, the heterozygous (NFAT5(+/-)) mice were used to study the in vivo role of NFAT5 in hypoxia/ischemia (H/I) condition. The NFAT5(+/-) mice exhibited more severe neurological deficits, larger infarct area and edema formation associated with increased aquaporin 4 expressions in the brain. Under in vitro H/I condition, increased apoptotic cell death was found in NFAT5(-/-) neurons. Moreover, SMIT, a downstream to NFAT5, was upregulated in NFAT5(+/+) neurons, while the SMIT level could not be upregulated in NFAT5(-/-) neurons under H/I condition. The elevation of reactive oxygen species generation in NFAT5(-/-) neurons under H/I condition further confirmed that NFAT5(-/-) neurons were more susceptible to oxidative stress. The present study demonstrated that activation of NFAT5 and its downstream SMIT induction is important in protecting neurons from ischemia-induced oxidative stress.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000331899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31064778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2011-11-09DOI: 10.1159/000330743
Lei Zhang, Juan Li, Nuyun Liu, Bin Wang, Jingjing Gu, Min Zhang, Zhitao Zhou, Yong Jiang, Lin Zhang, Lu Zhang
{"title":"Signaling via dopamine D1 and D3 receptors oppositely regulates cocaine-induced structural remodeling of dendrites and spines.","authors":"Lei Zhang, Juan Li, Nuyun Liu, Bin Wang, Jingjing Gu, Min Zhang, Zhitao Zhou, Yong Jiang, Lin Zhang, Lu Zhang","doi":"10.1159/000330743","DOIUrl":"https://doi.org/10.1159/000330743","url":null,"abstract":"<p><p>Repeated exposure to cocaine can induce persistent alterations in the brain. The structural remodeling of dendrites and dendritic spines is thought to play a critical role in cocaine addiction. We previously demonstrated that signaling via dopamine D1 and D3 receptors have opposite effects on cocaine-induced gene expression. Here, we show that cocaine-induced structural remodeling in the nucleus accumbens (NAc) and caudoputamen (CPu) is mediated by D1 receptors and inhibited by D3 receptors. In addition, chronic exposure to cocaine results in an altered number of asymmetric spine synapses via the actions of both D1 and D3 receptors. The contradictory effects of D1 and D3 receptor signaling on cocaine-induced structural remodeling is associated with NMDA-receptor R1 subunit (NR1) phosphorylation, and is dependent upon the activation of extracellular signal-regulated kinase (ERK). In addition, we found that D1 and D3 receptor signaling has contradictory effects upon the activation of the myocyte enhancer factor 2 (MEF2), which is involved in the dendritic remodeling after cocaine treatment. Together, these data suggest that dopamine D1 and D3 receptors differentially regulate the cocaine-induced structural remodeling of dendrites and spines via mechanisms involving the consecutive actions of NR1 phosphorylation, ERK activation, and MEF2 activity in the NAc and CPu.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000330743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30245471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2011-09-23DOI: 10.1159/000330193
Francisco J Monje, Eun-Jung Kim, Daniela D Pollak, Maureen Cabatic, Lin Li, Arthur Baston, Gert Lubec
{"title":"Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.","authors":"Francisco J Monje, Eun-Jung Kim, Daniela D Pollak, Maureen Cabatic, Lin Li, Arthur Baston, Gert Lubec","doi":"10.1159/000330193","DOIUrl":"https://doi.org/10.1159/000330193","url":null,"abstract":"<p><p>The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000330193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30170390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2012-03-27DOI: 10.1159/000333784
Jennifer Rodger, Lorena Salvatore, Paolo Migani
{"title":"Should I stay or should I go? Ephs and ephrins in neuronal migration.","authors":"Jennifer Rodger, Lorena Salvatore, Paolo Migani","doi":"10.1159/000333784","DOIUrl":"https://doi.org/10.1159/000333784","url":null,"abstract":"<p><p>In neuroscience, Ephs and ephrins are perhaps best known for their role in axon guidance. It was first shown in the visual system that graded expression of these proteins is instrumental in providing molecular coordinates that define topographic maps, particularly in the visual system, but also in the auditory, vomeronasal and somatosensory systems as well as in the hippocampus, cerebellum and other structures. Perhaps unsurprisingly, the role of these proteins in regulating cell-cell interactions also has an impact on cell mobility, with evidence that Eph-ephrin interactions segregate cell populations based on contact-mediated attraction or repulsion. Consistent with these studies, evidence has accumulated that Ephs and ephrins play important roles in the migration of specific cell populations in the developing and adult brain. This review focusses on two examples of neuronal migration that require Eph/ephrin signalling - radial and tangential migration of neurons in cortical development and the migration of newly generated neurons along the rostral migratory stream to the olfactory bulb in the adult brain. We discuss the challenge involved in understanding how cells determine whether they respond to signals by migration or axon guidance.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30536401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2012-05-04DOI: 10.1159/000334489
Clare Faux, Sonja Rakic, William Andrews, Joanne M Britto
{"title":"Neurons on the move: migration and lamination of cortical interneurons.","authors":"Clare Faux, Sonja Rakic, William Andrews, Joanne M Britto","doi":"10.1159/000334489","DOIUrl":"https://doi.org/10.1159/000334489","url":null,"abstract":"<p><p>The modulation of cortical activity by GABAergic interneurons is required for normal brain function and is achieved through the immense level of heterogeneity within this neuronal population. Cortical interneurons share a common origin in the ventral telencephalon, yet during the maturation process diverse subtypes are generated that form the characteristic laminar arrangement observed in the adult brain. The long distance tangential and short-range radial migration into the cortical plate is regulated by a combination of intrinsic and extrinsic signalling mechanisms, and a great deal of progress has been made to understand these developmental events. In this review, we will summarize current findings regarding the molecular control of subtype specification and provide a detailed account of the migratory cues influencing interneuron migration and lamination. Furthermore, a dysfunctional GABAergic system is associated with a number of neurological and psychiatric conditions, and some of these may have a developmental aetiology with alterations in interneuron generation and migration. We will discuss the notion of additional sources of interneuron progenitors found in human and non-human primates and illustrate how the disruption of early developmental events can instigate a loss in GABAergic function.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000334489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30606719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitric oxide and ATP-sensitive potassium channels mediate lipopolysaccharide-induced depression of central respiratory-like activity in brain slices.","authors":"An-Dong Lu, Jia-Feng Wang, Yong-Hua Chen, Li-Li Hou, Xu-Jiao Zhou, Jin-Jun Bian, Ji-Jiang Wang, Ke-ming Zhu","doi":"10.1159/000330841","DOIUrl":"https://doi.org/10.1159/000330841","url":null,"abstract":"<p><p>Infection may result in early abnormalities in respiratory movement, and the mechanism may involve central and peripheral factors. Peripheral mechanisms include lung injury and alterations in electrolytes and body temperature, but the central mechanisms remain unclear. In the present study, brainstem slices harvested from rats were stimulated with lipopolysaccharide at different doses. Central respiratory activities as demonstrated by electrophysiological activity of the hypoglossal rootlets were examined and the mechanisms were investigated by inhibiting nitric oxide synthase and ATP-sensitive potassium channels. As a result, 0.5 μg/ml lipopolysaccharide mainly caused inhibitory responses in both the frequency and the output intensity, while 5 μg/ml lipopolysaccharide caused an early frequency increase followed by delayed decreases in both the frequency and the output intensity. At both concentrations the inhibitory responses were fully reversed by inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (20 μM), and by inhibition of ATP- sensitive potassium channels with glybenclamide (100 μM). These results show that direct lipopolysaccharide challenge altered central respiratory activity in dose- and time- related manners. Nitric oxide synthase and ATP-sensitive potassium channels may be involved in the respiratory changes.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000330841","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30453720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2011-12-22DOI: 10.1159/000330805
Mathieu P Lichtenstein, José L M Madrigal, Aurora Pujol, Elena Galea
{"title":"JNK/ERK/FAK mediate promigratory actions of basic fibroblast growth factor in astrocytes via CCL2 and COX2.","authors":"Mathieu P Lichtenstein, José L M Madrigal, Aurora Pujol, Elena Galea","doi":"10.1159/000330805","DOIUrl":"https://doi.org/10.1159/000330805","url":null,"abstract":"<p><p>While the role of cytokines in causing pro- and anti-inflammatory cascades in the brain and that of chemokines in promoting chemotaxis is well recognized, the immunomodulatory actions of neurotrophins released during brain injury remains largely undetermined. This knowledge gap affects basic fibroblast growth factor (FGF2), which in the brain is mainly produced by astrocytes and characteristically upregulated in reactive astrocytes. The goal of this study was to characterize the inflammatory actions of FGF2 in astrocytes using primary cultures. We report that FGF2 induced the upregulation of monocyte chemoattractant protein (CCL2) and cyclo-oxygenase type 2 (COX2), and the inhibition of lipopolysaccharide-elicited ICAM1 upregulation. The effects of FGF2 were: (i) dependent on gene transcription as revealed by the concomitant regulation of CCL2 or ICAM1 mRNAs; (ii) mediated by the FGF2 receptor type 2; (iii) dependent on ERK, JNK and FAK, and (iv) NF-κB-independent. FGF2 also caused accelerated wound closure dependent on CCL2, COX2, ERK, JNK and FAK in a scratch assay. We conclude that the signaling network triggered by FGF2 in astrocytes converged into accelerating directed motion. It follows that astrocyte migration to injury sites may be a key factor in the repair mechanisms orchestrated by FGF2.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000330805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30341439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2012-01-28DOI: 10.1159/000334960
Nam Gyu Hyun, Kwang-Ho Hyun, Kyungmin Lee, Bong-Kiun Kaang
{"title":"Temperature dependence of action potential parameters in Aplysia neurons.","authors":"Nam Gyu Hyun, Kwang-Ho Hyun, Kyungmin Lee, Bong-Kiun Kaang","doi":"10.1159/000334960","DOIUrl":"https://doi.org/10.1159/000334960","url":null,"abstract":"<p><p>Although the effects of temperature changes on the activity of neurons have been studied in Aplysia, the reproducibility of the temperature dependence of the action potential (AP) parameters has not been verified. To this end, we performed experiments using Aplysia neurons. Fourteen AP parameters were analyzed using the long-term data series recorded during the experiments. Our analysis showed that nine of the AP parameters decreased as the temperature increased: the AP amplitude (A(AP)), membrane potential at the positive peak (V(pp)), interspike interval, first half (Δt(r1)) and last half (Δt(r2)) of the temperature rising phase, first half (Δt(f1)) and last half (Δt(f2)) of the temperature falling phase, AP (Δt(AP, 1/2)), and differentiated signal (Δt(DS, 1/2)) half-width durations. Five of the AP parameters increased with temperature: the differentiated signal amplitude (A(DS)), absolute value of the membrane potential at negative peak (|V(np)|), absolute value of the maximum slope of the AP during the temperature rising (|-MSR|) and falling (|MSF|) phases, and spiking frequency (Frequency). This work could provide the basis for a better understanding of the elementary processes underlying the temperature-dependent neuronal activity in Aplysia.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000334960","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30420107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeurosignalsPub Date : 2012-01-01Epub Date: 2011-10-19DOI: 10.1159/000330414
Aung Than, Yan Tan, Wei-Yi Ong, Akhlaq A Farooqui, Peng Chen
{"title":"Kainate receptors mediate regulated exocytosis of secretory phospholipase A(2) in SH-SY5Y neuroblastoma cells.","authors":"Aung Than, Yan Tan, Wei-Yi Ong, Akhlaq A Farooqui, Peng Chen","doi":"10.1159/000330414","DOIUrl":"https://doi.org/10.1159/000330414","url":null,"abstract":"<p><p>Secretory phospholipase A(2) (sPLA(2)) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA(2) (sPLA(2)-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA(2) is itself released, and a possible relation between glutamate receptors and sPLA(2) exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA(2)-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA(2)-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA(2)-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA(2)-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA(2)-IIA secretion. Moreover, KA-induced sPLA(2)-IIA secretion is dependent on Ca(2+) and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA(2) secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000330414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30085737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}